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Arterial and venous thrombosis constitute a major source of morbidity and mortality worldwide. Association between thrombotic complications and cardiovascular and other chronic inflammatory diseases are well described. Inflammation and subsequent initiation of thrombotic events, termed immunothrombosis, also receive growing attention but are still incompletely understood. Nevertheless, the clinical relevance of aberrant immunothrombosis, referred to as thromboinflammation, is evident by an increased risk of thrombosis and cardiovascular events in patients with inflammatory or infectious diseases. Proinflammatory mediators released from platelets, complement activation, and the formation of NETs (neutrophil extracellular traps) initiate and foster immunothrombosis. In this review, we highlight and discuss prominent and emerging interrelationships and functions between NETs and other mediators in immunothrombosis in cardiovascular disease. Also, with patients with chronic kidney disease suffering from increased cardiovascular and thrombotic risk, we summarize current knowledge on neutrophil phenotype, function, and NET formation in chronic kidney disease. In addition, we elaborate on therapeutic targeting of NETs-induced immunothrombosis. A better understanding of the functional relevance of antithrombotic mediators which do not increase bleeding risk may provide opportunities for successful therapeutic interventions to reduce thrombotic risk beyond current treatment options.

This retrieval study included 43 Biolox delta explants (18 CoC, 25 CoP). Implants were examined macroscopically, whereby damage was evaluated using a semi quantitative scoring system. Confocal microscopy was used to examine wear related damage patterns of the articulating surfaces. Scanning electron microscopy (SEM) with energy-dispersive X-ray spectroscopy (EDS) was used to analyze wear marks on the implant surface and wear debris in periprosthetic tissue samples. Raman spectroscopy and X-ray diffraction (XRD) were used to quantify monoclinic zirconia fractions. On all components, in vivo wear resulted predominantly in different damage patterns caused by metal transfer. In CoC bearings stripe wear was additionally detected, and some implants underwent severe damage due to component breakage. The wear scores were higher for CoC components, with no differences between the scores for CoC heads and liners. Wear features caused comparable roughening on implants from CoC and CoP bearings. SEM studies demonstrated that most wear marks were caused by metal debris released from implant components. Grain pull-out was observed in stripe wear regions. Monoclinic phase shift was observed in a similar quantity on components from CoP and CoC bearings. The increase of monoclinic zirconia content around metal deposits was minimal and was more pronounced in areas of stripe wear. The results of this study indicate, that ZTA components in general undergo minimal wear in both, CoC and CoP bearings, however, it is more pronounced in the former. Metal deposits, as the most common wear feature, have no significant effect on monoclinic phase transition. STATEMENT OF SIGNIFICANCE: : In this paper, we classify all damage patterns macroscopically according to an established scoring system and assess them regarding surface roughness (confocal microscopy) and monoclinic phase content (Raman spectroscopy) in order to derive the severity for patients. We compare hard-hard and hard-soft bearings and relate damage patterns with metal transfer based on SEM/EDS examinations. Furthermore, we work out correlations between patient-specific data, cause of revision and the physical condition of each individual sample Our cohort consists of 43 Biolox delta retrievals, a comparatively large quantity. In addition, we address current topics such as metal transfer and, based on the classification of damage patterns, provide incentives and/or meaningful focal points for further research.

The stainless steel must be treated as good material used to construction of antenna mounts. The duplex steel 1.4462 steel has a very good resistance to corrosion in an ambient and also in an elevated temperatures. The duplex steel is rather good weldable, although it is prone to various types of welding incompatibilities. Many factors influence quality of the weld. The goal of the paper is to study of the influence of main MAG welding parameters on creation of proper welds. A novelty in an article is the use of shielding gas mixtures with a very limited amount of oxygen (below 1% O2) in MAG welding. Welding duplex steels with a shielding gas mixture with a very low oxygen concentration was difficult until recently. It could be expected that new technological solution will allow to obtain a duplex joint with good corrosion resistance and good mechanical properties, which is important in antenna structures. The mechanical properties of several tested joints were investigated and the relationship between the oxygen content in the gas mixture and the oxygen content in the weld was determined.

Die ursprünglich als Transportkennel bezeichnete Hundebox hat sich mittlerweile als Erziehungshilfsmittel etabliert. Der Einsatz wird dabei als vorteilhaft für Mensch und Hund gesehen. Doch wie ist das tierschutzrechtlich zu beurteilen? Wir als Tierärzte und Tiertherapeuten tragen große Verantwortung für das Wohl der Hunde in unserer Gesellschaft. Wir sind für Hundebesitzer die ersten Ansprechpartner, wenn es um die Gesundheit und das Wohlergehen ihrer vierbeinigen Lieblinge geht. Wie kann man die Hundehalter dahingehend beraten? Welche gesetzlichen Vorgaben gibt es?

ZusammenfassungDie Arthrose des oberen Sprunggelenks stellt eine weitverbreitete degenerative Erkrankung der unteren Extremität dar. Obwohl sie in vielen Fällen auf eine vorhergehende Verletzung zurückgeführt werden kann, können auch chronisch-entzündliche Erkrankungen zu degenerativen Veränderungen des oberen Sprunggelenks führen. Nach umfangreicher Abklärung des Patienten zur Indikationsstellung kann die Sprunggelenksprothese im fortgeschrittenen Arthrosestadium als Behandlungsoption für Patienten gesehen werden, da die prothetische Versorgung sowohl die Lebensqualität und Funktion des Gelenks verbessert als auch Schmerzen lindert. Da es sich hierbei, im Vergleich zu anderen Endoprothesen, um eine seltene Operation handelt, ist eine umfangreiche präoperative Abklärung beim Spezialisten oder in einem spezialisierten Zentrum notwendig.

Recent studies point toward a significant impact of cardiovascular processes and inflammation on Parkinson's disease (PD) progression.The aim of this study was to assess established markers of neuronal function, inflammation, and cardiovascular risk by high-throughput sandwich immune multiplex panels in deeply phenotyped PD.Proximity Extension Assay technology on 273 markers was applied in plasma of 109 drug-naive at baseline (BL) patients with PD (BL, 2-, 4-, and 6-year follow-up [FU]) and 96 healthy control patients (HCs; 2- and 4-year FU) from the de novo Parkinson's cohort. BL plasma from 74 individuals (37 patients with PD, 37 healthy control patients) on the same platform from the Parkinson Progression Marker Initiative was used for independent validation. Correlation analysis of the identified markers and 6 years of clinical FU, including motor and cognitive progression, was evaluated.At BL, 35 plasma markers were differentially expressed in PD, showing downregulation of atherosclerotic risk markers, eg, E-selectin and ßWe identified and validated possible PD plasma biomarker candidates for state, fate, and disease progression, elucidating new molecular processes with reduced endothelial/atherosclerotic processes, increased thromboembolic risk, and neuroinflammation. Further investigations and validation in independent and larger longitudinal cohorts are needed. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Parkinson’s disease (PD) is defined by its motor symptoms rigidity, tremor, and akinesia. However, non-motor symptoms, particularly autonomic disorders and sleep disturbances, occur frequently in PD causing equivalent or even greater discomfort than motor symptoms effectively decreasing quality of life in patients and caregivers. Most common sleep disturbances in PD are insomnia, sleep disordered breathing, excessive daytime sleepiness, REM sleep behavior disorder, and sleep-related movement disorders such as restless legs syndrome. Despite their high prevalence, therapeutic options in the in- and outpatient setting are limited, partly due to lack of scientific evidence. The importance of sleep disturbances in neurodegenerative diseases has been further emphasized by recent evidence indicating a bidirectional relationship between neurodegeneration and sleep. A more profound insight into the underlying pathophysiological mechanisms intertwining sleep and neurodegeneration might lead to unique and individually tailored disease modifying or even neuroprotective therapeutic options in the long run. Therefore, current evidence concerning the management of sleep disturbances in PD will be discussed with the aim of providing a substantiated scaffolding for clinical decisions in long-term PD therapy.

ZusammenfassungDer vorliegende Praxisbeitrag befasst sich mit der Kurzvideoplattform TikTok. Er beschreibt die Funktionsweise der Plattform und geht auf den bisherigen Stand der TikTok-Forschung ein. Im Fokus stehen dann Sexualaufklärung, LGBTIQ + sowie Beziehungs- und Datingberatung auf TikTok.

Background Endoscopic vacuum therapy (EVT) is an effective treatment option for leakage of the upper gastrointestinal (UGI) tract. The aim of this study was to evaluate the clinical impact of quality improvements in EVT management on patients’ outcome. Methods All patients treated by EVT at our center during 2012–2021 were divided into two consecutive and equal-sized cohorts (period 1 vs. period 2). Over time several quality improvement strategies were implemented including the earlier diagnosis and EVT treatment and technical optimization of endoscopy. The primary endpoint was defined as the composite score MTL30 (mortality, transfer, length-of-stay > 30 days). Secondary endpoints included EVT efficacy, complications, in-hospital mortality, length-of-stay (LOS) and nutrition status at discharge. Results A total of 156 patients were analyzed. During the latter period the primary endpoint MTL30 decreased from 60.8 to 39.0% (P = .006). EVT efficacy increased from 80 to 91% (P = .049). Further, the need for additional procedures for leakage management decreased from 49.9 to 29.9% (P = .013) and reoperations became less frequent (38.0% vs.15.6%; P = .001). The duration of leakage therapy and LOS were shortened from 25 to 14 days (P = .003) and 38 days to 25 days (P = .006), respectively. Morbidity (as determined by the comprehensive complication index) decreased from 54.6 to 46.5 (P = .034). More patients could be discharged on oral nutrition (70.9% vs. 84.4%, P = .043). Conclusions Our experience confirms the efficacy of EVT for the successful management of UGI leakage. Our quality improvement analysis demonstrates significant changes in EVT management resulting in accelerated recovery, fewer complications and improved functional outcome.

Organic and biodynamic management practices in viticulture have been sharply increasing worldwide for almost two decades and are seen as one possibility for environmentally friendly production. Consumers often presume that the quality of organically grown crops is different or higher compared to conventionally grown crops.In the current study, wine grape quality under integrated, organic and biodynamic viticulture was assessed in a long-term field trial in Geisenheim, Germany, starting seven years after conversion. Treatments substantially differed in their amino acid concentration in juice, flavonol content and their composition of hydroxycinnamic acids. Organic and biodynamic treatments showed significantly higher concentrations of all amino acids in juice and a significantly higher concentration of flavonols in berry skins. Major drivers of these changes are reductions of yield and pruning weight under organic and biodynamic management on the one hand and increased light exposure of bunches in the respective treatments on the other hand.Linking amino acid composition in juice, grape skin flavonoid and hydroxycinnamate concentration to canopy structure, vigour and yield enables growers to actively control and manipulate wine grape quality in the different management systems.

Metastasis, a complex, multistep process, is responsible for the overwhelming majority of cancer-related deaths. Despite its devastating consequences, it is not possible to effectively treat cancer that has spread to vital organs, the mechanisms leading to metastasis are still poorly understood, and the catalog of metastasis promoting genes is still incomprehensive. To identify new driver genes of metastasis development, we performed an in vitro Sleeping Beauty transposon-based forward genetic screen in nonmetastatic SKBR3 human breast cancer cells. Boyden chamber-based matrix invasion assays were used to harvest cells that acquired a de novo invasive phenotype. Using targeted RNA sequencing data from 18 pools of invasive cells, we carried out a gene-centric candidate gene prediction and identified established and novel metastasis driver genes. Analysis of these genes revealed their association with metastasis related processes and we further established their clinical relevance in metastatic breast cancer. Two novel candidate genes, G protein–coupled receptor kinase interacting ArfGAP 2 (GIT2) and muscle-associated receptor tyrosine kinase (MUSK), were functionally validated as metastasis driver genes in a series of in vitro and in vivo experimental metastasis models. We propose that our robust and scalable approach will be a useful addition to the toolkit of methodologic resources used to identify genes driving cancer metastasis. Implications: Novel metastasis drivers were identified in a human breast cancer cell line by performing an in vitro, Sleeping Beauty transposon-based forward genetic screen and an RNA fusion-based candidate gene prediction.

ZusammenfassungDieser Praxisbeitrag stellt den Slow-Sex-Ansatz vor. Slow Sex meint einen entschleunigten, entspannten und achtsamen sexuellen Kontakt, der keine besonderen Anstrengungen erfordert: Man muss keine Erregung mitbringen, keine neuen Techniken meistern und keine Orgasmen erreichen. Das klingt vielleicht zunächst etwas langweilig. Slow-Sex-Erfahrene berichten jedoch von ausgesprochen belebenden, beglückenden und verbindenden Begegnungen – und von spirituellen Erfahrungen.

Sex toys are widely marketed on the Internet. Browsing for, buying, and reviewing sex toys online are popular cybersexual activities. The aim of this study was to investigate consumers’ experiences with different types of realistic sex toys via online product reviews on Amazon.com. Toys were categorized in a 2 × 2 design regarding their representation of the human body (genitalia sex toys representing reproductive organs only versus torso toys representing larger parts of the human body) and their depiction of gender (toys representing female versus male body parts). Informed by feminist discourses on sex toys as well as sexual script theory and consumer research, the study explored the overall evaluations (RQ1), most frequently addressed characteristics (RQ2), usage patterns (RQ3), and perceived effects (RQ4) of the four groups of sex toys. A quantitative manual content analysis of N = 778 online sex toy reviews showed that 79% of consumers gave popular realistic sex toys positive ratings (RQ1). The most frequently mentioned characteristics were quality, material, and shape (RQ2). Most reviewers were men and used sex toys for solo sexual activities (RQ3). An additional qualitative analysis of n = 69 reviews addressing the perceived effects of sex toy use revealed that consumers predominantly mentioned positive effects (RQ4). Genitalia sex toys received better evaluations than torso sex toys and were perceived to be complementary tools to enhance sexual arousal, whereas the use of torso toys entailed anthropomorphization and symbolic social interactions. Implications for future research and design of different types of sex toys are discussed.

Ein halbes Jahrhundert ist es her, dass die Sexualaufklärerin und Mitbegründerin des sexpositiven Feminismus Betty Dodson in den 1970er-Jahren begann, öffentlich über weibliche Genitalien und Selbstbefriedigung zu sprechen. In Bettys Bodysex-Workshops erkundeten Frauen* gemeinsam ihre Lust, nackt im Kreis auf dem Boden sitzend. Ihr Buch „Liberating Masturbation: A Meditation in Selflove“ (1974) machte international Furore, es erschien auch auf Deutsch. Und nicht nur schwang Betty Dodson zu Zeiten der sexuellen Revolution und zweiten Frauenbewegung öffentlich den Vibrator, sie machte mit ihren realistischen Fotos und Zeichnungen von Vulven, die u. a. auf Konferenzen präsentiert wurden, auf die Schönheit und Vielfalt der äußeren weiblichen Genitalien aufmerksam (https://dodsonandross.com/vulva).

Zusammenfassung Einleitung Seit den 1960er-Jahren wird in Wissenschaft, Frauenbewegung und breiter Öffentlichkeit darüber diskutiert, dass und warum Frauen beim Heterosex seltener Orgasmen erleben als Männer und ob und wie man diesen Gender Orgasm Gap schließen kann. Im Rahmen eines bio-psycho-sozialen Verständnisses von Sexualität werden Gender Orgasm Gaps theoretisch sehr unterschiedlich erklärt. Forschungsziele Ziel des vorliegenden Forschungsüberblicks ist es, die bisherigen empirischen Befunde zur Größe des Gender Orgasm Gap zu berichten sowie die vorgeschlagenen Praxismaßnahmen zu seiner Überwindung zu präsentieren und kritisch zu diskutieren. Methoden Im Zuge einer systematischen Literaturrecherche wurden n = 20 empirische Publikationen zum Gender Orgasm Gap und zusätzlich n = 16 wissenschaftliche Originalarbeiten zu seinem Abbau identifiziert und kodiert (1982–2021). Ergebnisse Die eingeschlossenen Umfragen basieren auf Angaben von N = 49 940 Frauen und N = 48 329 Männern und zeigen, dass typischerweise 30 % bis 60 % der befragten Frauen berichten, beim Heterosex zum Orgasmus zu kommen, im Unterschied zu 70 % bis 100 % der Männer. Je nach Rahmenbedingungen des Heterosex schwankt die Größe des Gender Orgasm Gap zwischen –20 % und –72 % zuungunsten der Frauen. Die vorliegenden zehn bevölkerungsrepräsentativen Umfragen ergeben einen gewichteten mittleren Gender Orgasm Gap von –30 % [95 %iges Konfidenzintervall: –31 %; –30 %]. Die in der bisherigen Fachliteratur vorgeschlagenen Maßnahmen zum Schließen dieser Orgasmus-Lücke beziehen sich auf personale Faktoren, Beziehungsfaktoren, sexuelle Interaktionsfaktoren und gesellschaftliche Faktoren: Frauen wird empfohlen, den eigenen Orgasmus bewusster anzustreben und in der Beziehung offener über sexuelle Wünsche zu sprechen. Zudem wird Frauen und Männern geraten, mehr direkte klitorale Stimulation in den Heterosex zu integrieren und Orgasmen von Frauen gesellschaftlich zu demarginalisieren. Schlussfolgerung Aus dem bisherigen Forschungsstand leitet sich die Notwendigkeit ab, Fragen rund um den Gender Orgasm Gap weiterhin in Wissenschaft und Praxis zu bearbeiten. Angesichts der begrenzten Erfolge der letzten Dekaden scheint es jedoch auch geboten, die bisher verfolgten Ansätze im „Kampf um Orgasmus-Gerechtigkeit“ kritisch zu hinterfragen.

The high spin states in 61 Ni have been studied using the fusion evaporation reaction, Ti( $^{14}$C,3n) $^{61}$Ni at an incident beam energy of 40 MeV. A Compton suppressed multi-HPGe detector setup, consisting of six Clover detectors and three single crystal HPGe detectors was used to detect the de-exciting $\gamma$ rays from the excited states. The level scheme has been extended up to an excitation energy of 12.8 MeV and a tentative J$_{\pi}$ = 35/2$^+$ . The low-lying negative parity levels are found to be generated by single particle excitation within the f p shell and also excitations to the g$_{9/2}$ orbitals as explained well with shell model calculations using the GXPF1Br+V M U (modified) interaction. Two rotational structure of regular E2 sequences with small to moderate axial deformation have been established at higher excitation energy. Most interestingly, two sequences of M1 transitions are reported for the first time and described as magnetic rotational bands. The shears mechanism for both the bands can be described satisfactorily by the geometrical model. The shell model calculation involving the cross shell excitation beyond the fp shell well reproduce the M1 and E2 sequences. The shell model predicted B(M1) values for the magnetic rotational band B1 show the decreasing trend with spin as expected with closing of the shears., Comment: 18 pages, 17 Fig

Practicing mindfulness is associated with stress reduction and with positive effects in the context of learning and teaching. Although effects on student populations have been studied extensively, there are few studies implementing mindfulness exercises in university courses directly. For this reason, we aimed to investigate whether the use of a brief mindfulness exercise in regular university courses, guided by the lecturers, is feasible and has immediate effects on the students’ mental states. We conducted a preregistered multicenter study with one observational arm, following an ABAB design. In total, N = 325 students from 19 different university courses were included at baseline and n = 101 students at post measurement. Students were recruited by N = 14 lecturers located in six different universities in Germany. Lecturers started their courses either by guiding a brief mindfulness exercise (intervention condition) or as they regularly would, with no such exercise (control condition). In both conditions, the mental states of students and lecturers were assessed. Over the semester, n = 1193 weekly observations from students and n = 160 observations from lecturers were collected. Intervention effects were analyzed with linear mixed-effects models. The brief mindfulness exercise, compared to no such exercise, was associated with lower stress composite scores, higher presence composite scores, higher motivation for the courses, as well as better mood in students. Effects persisted throughout a respective course session. Lecturers also reported positive effects of instructing mindfulness. Implementing a brief mindfulness exercise in regular university teaching sessions is feasible and has positive effects on both students and lecturers.

To overcome threats to agro-ecosystems, such as a dramatic species decline, an ecological intensification in crop production is needed. One possible strategy is the simultaneous cultivation of legume and cereal plants in a mixed arrangement, namely mixed cropping. Cereal-legume crop mixtures may benefit from diversity effects, i.e. improved use of environmental resources such as light, water and nitrogen. Thus, mixtures have shown to result in higher land productivity with respect to grain yield compared to sole cropping. However, mixture systems are complex and difficult to study due to dynamic species interactions and their heterogeneous canopy structures. To better understand structural and functional diversity effects in a mixed cropping system, we non-invasively studied two crops in a field trial in 2021 and 2022. Here, different genotypes of faba bean (Vicia faba L.) and spring wheat (Triticum aestivum L.) were combined in six legume-cereal mixtures. The 1:1 mixtures were compared to each other and against the respective sole crops. To study structural and functional diversity effects in mixtures, we applied proximal and remote sensing tools. We characterized photosynthesis-related plant traits derived from hyperspectral and solar-induced fluorescence (SIF) data recorded with ground-based and airborne sensors. The high-performance airborne spectrometer HyPlant was used to acquire SIF image data with 1 m spatial resolution. Additionally, we collected hyperspectral and SIF point measurements with the mobile field sensor system FloX on different dates during the two growing seasons. We found that HyPlant and FloX datasets of different mixtures and crop types collected in mid-June showed significantly different levels of far-red SIF emission efficiency (εF) (p

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.

Behavioral manipulation (BM) is a multimodal control approach based on the interference with the stimuli mediating insect perception and interaction with the surroundings. BM could represent a win–win strategy for the management of vector-borne plant pathogens as the bacterium Xylella fastidiosa, since it could reduce the number of vectors alighting on host plants and, consequently, the chances for transmission to occur. In this review, we summarized current knowledge and highlighted gaps in information on (i) how insect vectors of X. fastidiosa in general, and more specifically the meadow spittlebug Philaenus spumarius, locate and accept the host plant; and (ii) how behavioral manipulation techniques could be applied to disrupt the vector–host plant interaction. Finally, we discussed how diverse BM strategies could be combined with other integrated pest management tools to protect olive groves from inoculation with the fastidious bacterium.

Zusammenfassung Hintergrund Jugendliche und Erwachsene beziehen Informationen über Verhütung zunehmend über soziale Medien. Ziel der Arbeit Vor diesem Hintergrund ist es Ziel der vorliegenden Studie, erstmals Inhalte und Qualität deutschsprachiger Verhütungsbeiträge auf YouTube, Instagram und TikTok zu untersuchen. Beantwortet werden sollen Forschungsfragen zu Anbieter*innen (F1), Inhalten (F2) und Qualität der Verhütungsbeiträge (F3) sowie zu Publikumsreaktionen (F4). Material und Methoden Es wurde eine Stichprobe von N = 1000 Verhütungsbeiträgen von YouTube (500), Instagram (250) und TikTok (250) gezogen. Pro Beitrag gingen maximal 20 verhütungsbezogene Kommentare in das Kommentar-Sample ein (N = 12.454). Die Beiträge und Kommentare wurden mittels reliabilitätsgeprüfter Codebücher analysiert. Die Datenanalyse erfolgte mit SPSS. Die Studie ist präregistriert und alle Daten, Materialien und Analyseskripte sind öffentlich verfügbar. Ergebnisse Es zeigte sich, dass die Verhütungsbeiträge mehrheitlich von Gesundheitslaien stammten (52 %), gefolgt von Medienprofis und Gesundheitsprofis (F1). Inhaltlich deckten die Verhütungsbeiträge alle verfügbaren Verhütungsmethoden ab, wobei Pille (69 %) und Kondom (40 %) dominierten (F2). Nach gängigen Qualitätskriterien zeigten sich deutliche Defizite, wobei im Vergleich YouTube-Videos am besten abschnitten (F3). TikTok-Videos dagegen waren Spitzenreiter bei den Publikumsreaktionen, sie verzeichneten die meisten Views, Likes und Kommentare. Die Kommentarspalten wurden vom Publikum oft genutzt, um eigene Verhütungserfahrungen zu teilen oder Nachfragen zu stellen (F4). Diskussion Weitere Forschung sowie Praxismaßnahmen sind notwendig, um die Qualität von Verhütungsinformationen in sozialen Medien besser einschätzen und optimieren zu können.

0AbstractWhole genome sequencing (WGS) at high-depth (30X) allows the accurate discovery of variants in the coding and non-coding DNA regions and helps elucidate the genetic underpinnings of human health and diseases. Yet, due to the prohibitive cost of high-depth WGS, most large-scale genetic association studies use genotyping arrays or high-depth whole exome sequencing (WES). Here we propose a novel, cost-effective method, which we call “Whole Exome Genome Sequencing” (WEGS), that combines low-depth WGS and high-depth WES with up to 8 samples pooled and sequenced simultaneously (multiplexed). We experimentally assess the performance of WEGS with four different depth of coverage and sample multiplexing configurations. We show that the optimal WEGS configurations are 1.7-2.0 times cheaper than standard WES (no-plexing), 1.8-2.1 times cheaper than high-depth WGS, reach similar recall and precision rates in detecting coding variants as WES, and capture more population-specific variants in the rest of the genome that are difficult to recover when using genotype imputation methods. We apply WEGS to 862 patients with peripheral artery disease and show that it directly assesses more known disease-associated variants than a typical genotyping array and thousands of non-imputable variants per disease-associated locus.

Chimeric antigen receptors (CARs) have improved cancer immunotherapy in recent years. Immune cells, such as Natural killer cells (NK-cells) or T cells, are used as effector cells in CAR-therapy. NK92-cells, a cell line with known cytotoxic activity, are of particular interest in CAR-therapy since culturing conditions are simple and anti-tumor efficacy combined with a manageable safety profile was proven in clinical trials. The major pathways of immune effector cells, including NK92-cells, to mediate cytotoxicity, are the perforin/granzyme and the death-receptor pathway. Detailed knowledge of CAR-effector cells’ cytotoxic mechanisms is essential to unravel resistance mechanisms, which potentially arise by resistance against apoptosis-inducing signaling. Since mutations in apoptosis pathways are frequent in lymphoma, the impact on CAR-mediated cytotoxicity is of clinical interest. In this study, knockout models of CD19-CAR-NK92 cells were designed, to investigate cytotoxic pathways in vitro. Knockout of perforin 1 (Prf1) and subsequent abrogation of the perforin/granzyme pathway dramatically reduced the cytotoxicity of CD19-CAR-NK92 cells. In contrast, knockout of FasL and inhibition of TRAIL (tumor necrosis factor-related apoptosis-inducing ligands) did not impair cytotoxicity in most conditions. In conclusion, these results indicate the perforin/granzyme pathway as the major pathway to mediate cytotoxicity in CD19-CAR-NK92 cells.

Purpose Wearables serve to quantify the on-court activity in intermittent sports such as field hockey (FH). Based on the objective data, benchmarks can be elaborated to tailor training intensity and volume. Next to average and accumulated values, the most intense periods (MIPs) during competitive FH matches are from special interest, since these quantify the peak intensities players experience throughout the intermittent matches. The aim of this study was to retrospectively compare peak intensities between training and competition sessions in a male FH team competing in the first german division. Methods Throughout an 8-week in-season period, 372 individual activity datasets (144 datasets from competitive sessions) were recorded using the Polar Team Pro sensor (Kempele, Finland). MIPs were calculated applying a rolling window approach with predefined window length (1 to 5 minutes) and calculated for Total distance, High-Intensity-Running distance (> 16 km/h), Sprinting distance (> 20 km/h) and Acceleration load. Significant differences between training and competition MIPs were analysed through unpaired t-tests (p

Zusammenfassung Einleitung Jugendliche und junge Erwachsene beziehen Informationen über Methoden der Schwangerschafts- bzw. Zeugungsverhütung heute oft aus dem Internet und insbesondere aus Sozialen Medien wie YouTube, Instagram oder TikTok. Forschungsziele Bislang ist jedoch kaum untersucht worden, wie diese Nutzung von Social-Media-Verhütungsinformationen bei jungen Menschen im Einzelnen beschaffen ist (Forschungsfrage 1). Unklar ist auch, wie junge Menschen verhütungsbezogene Beiträge (F2) und zugehörige Publikumskommentare (F3) bewerten und welche Anforderungen sie an eine gute Verhütungsaufklärung in Sozialen Medien stellen (F4). Methoden Zur Beantwortung dieser vier Forschungsfragen wurde im Jahr 2022 eine präregistrierte qualitative Interviewstudie durchgeführt. Dabei wurde eine Stichprobe von N = 12 cisgeschlechtlichen heterosexuellen Jugendlichen und jungen Erwachsenen (17 bis 25 Jahre, 50 % weiblich und 50 % männlich) im Zuge von Leitfaden-Interviews (durchschnittliche Dauer: 39 Minuten) befragt. Die Interviews wurden vollständig transkribiert und mit der qualitativen Datenanalyse-Software MAXQDA codiert. Ergebnisse Es zeigte sich, dass die Befragten in Sozialen Medien kaum gezielt nach Verhütungsinformationen suchten, sondern diese hauptsächlich im Push-Modus zugespielt bekamen, was dann aber zu weiterer Informationssuche anregen konnte (F1). Die Befragten bewerteten Verhütungsbeiträge in Sozialen Medien vor allem dann positiv, wenn diese von Fachleuten stammten und eine hohe Informationsqualität aufwiesen (F2). Die Publikumskommentare zu den Verhütungsbeiträgen wurden als interessant und relevant eingestuft, allerdings ließen sich die Befragten nach eigenen Angaben durch diese kaum in ihren verhütungsbezogenen Einstellungen beeinflussen (F3). Als ideale Verhütungsaufklärung in Sozialen Medien wünschten sich die Befragten zielgruppengerecht aufgearbeitete Erklärvideos von Fachleuten, die verschiedene Verhütungsmethoden vergleichen und in die auch authentische positive wie negative Erfahrungsberichte von Peers integriert sind (F4). Schlussfolgerung Aus den Befunden ergibt sich der Bedarf, Verhütungsaufklärung entsprechend der dargelegten Anforderungen in Sozialen Medien bereitzustellen. Auch sollte ein kritisch-konstruktiver Umgang mit Social-Media-Verhütungsinformationen in sexualpädagogischen Maßnahmen aufgegriffen werden.

Supplementary Figure from In Vitro Insertional Mutagenesis Screen Identifies Novel Genes Driving Breast Cancer Metastasis

Supplementary figures 1-5, supplementary tables 1-9

Follicular dendritic cell (FDC) sarcomas are rare mesenchymal tumors with variable clinical, morphologic, and phenotypic characteristics. Transcriptome analysis was performed on multiple FDC sarcomas and compared with other mesenchymal tumors, microdissected Castleman FDCs, and normal fibroblasts. Using unsupervised analysis, FDC sarcomas clustered with microdissected FDCs, distinct from other mesenchymal tumors and fibroblasts. The specific endowment of FDC-related gene expression programs in FDC sarcomas emerged by applying a gene signature of differentially expressed genes (n = 1,289) between microdissected FDCs and fibroblasts. Supervised analysis comparing FDC sarcomas with microdissected FDCs and other mesenchymal tumors identified 370 and 2,927 differentially expressed transcripts, respectively, and on the basis of pathway enrichment analysis ascribed to signal transduction, chromatin organization, and extracellular matrix organization programs. As the transcriptome of FDC sarcomas retained similarity with FDCs, the immune landscape of FDC sarcoma was investigated by applying the CIBERSORT algorithm to FDC sarcomas and non-FDC mesenchymal tumors and demonstrated that FDC sarcomas were enriched in T follicular helper (TFH) and T regulatory (TREG) cell populations, as confirmed in situ by immunohistochemistry. The enrichment in specific T-cell subsets prompted investigating the mRNA expression of the inhibitory immune receptor PD-1 and its ligands PD-L1 and PD-L2, which were found to be significantly upregulated in FDC sarcomas as compared with other mesenchymal tumors, a finding also confirmed in situ. Here, it is demonstrated for the first time the transcriptional relationship of FDC sarcomas with nonmalignant FDCs and their distinction from other mesenchymal tumors.Implications: The current study provides evidence of a peculiar immune microenvironment associated with FDC sarcomas that may have clinical utility. Mol Cancer Res; 15(5); 541–52. ©2017 AACR.

Das Papier „Ansatz für ein partnerschaftliches Forschungsdatenmanagement – Konzept für eine schleswig-holsteinische Landesinitiative zum Forschungsdatenmanagement“ stellt Aufgaben, Arbeitsweise, Organisation sowie Zuständigkeiten für die schleswig-holsteinische Landesinitiative zum Forschungsdatenmanagement FDM-SH vor.

A coupled-channel S- and P-wave next-to-leading order chiral-unitary approach for strangeness $S=-1$ meson-baryon scattering is extended to include the new data from the KLOE and AMADEUS experiments as well as the $Λπ$ mass distribution of the $Σ(1385)$. The positions of the poles on the second Riemann sheet corresponding to the $Σ(1385)$ pole and the $Λ(1380)$ and $Λ(1405)$ poles as well as the couplings of these states to various channels are calculated. We find that the resonance positions and branching ratios are on average determined with about 20\% higher precision when including the KLOE and AMADEUS data. Additionally, for the first time, the correlations between the parameters of the poles are investigated and shown to be relevant. We also find that the $Σ(1385)$ has negligible influence on the properties of the $Λ$ states given the available data. Still, we identify isospin-1 cusp structures in the present solution in light of new measurements of $π^\pmΛ$ line-shapes by the Belle collaboration., 21 pages, 6 figures

IntroductionIn immunocompromised patients, Epstein-Barr virus (EBV) infection or reactivation is associated with increased morbidity and mortality, including the development of B-cell lymphomas. The first-line treatment consists of reduction of immunosuppression and administration of rituximab (anti-CD20 antibody). Furthermore, the presence of EBV-specific T cells against latent EBV proteins is crucial for the control of EBV-associated diseases. Therefore, in addition to effective treatment strategies, appropriate monitoring of T cells of high-risk patients is of great importance for improving clinical outcome. In this study, we hypothesized that rituximab-mediated lysis of malignant EBV-infected B cells leads to the release and presentation of EBV-associated antigens and results in an augmentation of EBV-specific effector memory T-cell responses.MethodsEBV-infected B lymphoblastoid cell lines (B-LCLs) were used as a model for EBV-associated lymphomas, which are capable of expressing latency stage II and III EBV proteins present in all known EBV-positive malignant cells. Rituximab was administered to obtain cell lysates containing EBV antigens (ACEBV). Efficiency of cross-presentation of EBV-antigen by B-LCLs compared to cross-presentation by professional antigen presenting cells (APCs) such as dendritic cells (DCs) and B cells was investigated by in vitro T-cell immunoassays. Deep T-cell profiling of the tumor-reactive EBV-specific T cells in terms of activation, exhaustion, target cell killing, and cytokine profile was performed, assessing the expression of T-cell differentiation and activation markers as well as regulatory and cytotoxic molecules by interferon-γ (IFN-γ) EliSpot assay, multicolor flow cytometry, and multiplex analyses.ResultsBy inhibiting parts of the cross-presentation pathway, B-LCLs were shown to cross-present obtained exogenous ACEBV-derived antigens mainly through major histocompatibility complex (MHC) class I molecules. This mechanism is comparable to that for DCs and B cells and resulted in a strong EBV-specific CD8+ cytotoxic T-cell response. Stimulation with ACEBV-loaded APCs also led to the activation of CD4+ T helper cells, suggesting that longer peptide fragments are processed via the classical MHC class II pathway. In addition, B-LCLs were also found to be able to take up exogenous antigens from surrounding cells by endocytosis leading to induction of EBV-specific T-cell responses although to a much lesser extent than cross-presentation of ACEBV-derived antigens. Increased expression of activation markers CD25, CD71 and CD137 were detected on EBV-specific T cells stimulated with ACEBV-loaded APCs, which showed high proliferative and cytotoxic capacity as indicated by enhanced EBV-specific frequencies and increased secretion levels of cytotoxic effector molecules (e.g. IFN-γ, granzyme B, perforin, and granulysin). Expression of the regulatory proteins PD-1 and Tim-3 was induced but had no negative impact on effector T-cell functions.ConclusionIn this study, we showed for the first time that rituximab-mediated lysis of EBV-infected tumor cells can efficiently boost EBV-specific endogenous effector memory T-cell responses through cross-presentation of EBV-derived antigens. This promotes the restoration of antiviral cellular immunity and presents an efficient mechanism to improve the treatment of CD20+ EBV-associated malignancies. This effect is also conceivable for other therapeutic antibodies or even for therapeutically applied unmodified or genetically modified T cells, which lead to the release of tumor antigens after specific cell lysis.

ZusammenfassungUnter hartem Sex (engl. rough sex) wird aggressiver konsensueller Sex verstanden. Dazu gehören beispielsweise Aktivitäten wie Aufs-Bett-Werfen, Kleider-Herunterreißen, Haare-Ziehen, Schlagen oder Würgen. Rough-Sex-Praktiken sind in den letzten Jahren medial sichtbarer und vermutlich auch populärer geworden. Ihnen sind ganze Pornografie-Gattungen gewidmet und sie werden in Sozialen Medien diskutiert. Große Bevölkerungsteile berichten eigene Erfahrungen mit ausgewählten harten Sexpraktiken. Die Normalisierung von Rough Sex wird mit verschiedenen Gefahren, insbesondere für Frauen, in Verbindung gebracht. Der vorliegende Beitrag fasst den aktuellen Diskussionsstand zusammen, weist auf Forschungslücken hin und diskutiert Konsequenzen für die sexualpädagogische Praxis.

Das Papier "Grundlagen eines partnerschaftlichen Forschungsdatenmanagements - Anforderungen an eine schleswig-holsteinische Landesinitiative zum Forschungsdatenmanagement" umreißt die Anforderungen für eine schleswig-holsteinische Landesinitiative zum Forschungsdatenmanagement (FDM-SH). Hierfür wird zunächst das Umfeld, in dem eine solche Initiative entstehen und agieren soll, beschrieben. So beeinflussen sowohl die Eigenheiten der regionalen Forschungslandschaft wie auch die Entwicklungen im Bereich der Nationalen Forschungsdateninfrastruktur (NFDI) die Ausprägungen von Landesinitiativen. Die speziellen Anforderungen werden durch den Vergleich mit anderen Landesinitiativen, die Analyse von spezifischen Umfrageergebnissen aus Schleswig-Holstein sowie die Berücksichtigung der Anforderungen der NFDI gesammelt. Der Ansatz des partnerschaftlichen Forschungsdatenmanagements (FDM) spiegelt das Anliegen Schleswig-Holsteins wider, die Herausforderungen für ein zeitgemäßes FDM vor Ort gemeinsam zu bewältigen und dabei sowohl Know-how zu teilen als auch Ressourcen zu schonen.