Search

Was ist neu? Epidemiologie In einer aktuellen epidemiologischen Arbeit zeigt sich ein seit 2013 rückläufiger Trend von Clostridioides-difficile-Infektionen (CDI) in Deutschland, zusammen mit einer Abnahme des Anteils hypervirulenter Ribotypen (vor allem RT 027 und RT 078). Dennoch bleibt die Krankheitslast hoch und insbesondere ältere und vorerkrankte Patientinnen und Patienten sind häufig betroffen. Aktuelle US-amerikanische Daten zeigen, dass bei älteren Patientinnen und Patienten insbesondere CDI-Rezidive, assoziierte psychiatrische Diagnosen wie Depressionen sowie Folgeerkrankungen wie Sepsis eine hohe Krankheitslast für Betroffene darstellen. Mikrobiologie Neue Studien liefern Erkenntnisse zum Zusammenspiel von C. difficile mit anderen Darmpathogenen; so scheinen Koinfektionen mit Enterokokken zu einer erhöhten Virulenz von C. difficile beizutragen. Neue europäische Therapieleitlinie Nach der 2021 aktualisierten ESCMID-Leitlinie ist Fidaxomicin aufgrund des geringeren Rezidivrisikos Mittel der ersten Wahl für erstmalig auftretende und rezidivierende CDI. Metronidazol dagegen sollte nur dann zum Einsatz kommen, wenn weder Fidaxomicin noch Vancomycin zur Verfügung stehen. Die fäkale Mikrobiota-Transplantation (FMT) hat sich im Rahmen eines individuellen Heilversuchs zur Behandlung mehrfach rezidivierender CDI etabliert; allerdings wurden die regulatorischen Auflagen dafür im Zuge der Corona-Pandemie weiter verschärft. Auch bei refraktär verlaufender fulminanter CDI kann die FMT als Alternative zur chirurgischen Intervention erwogen werden. Weitere Behandlungsmöglichkeiten Mit dem Small-Molecule-Antibiotikum Ridinilazol könnte in Zukunft neben Fidaxomicin ein weiteres CDI-Antibiotikum mit schmalem Wirkspektrum und kaum enteraler Resorption zur Verfügung stehen. Die orale Mikrobiota-Therapie mittels aufgereinigter Firmicutes-Sporen (SER-109) zeigte in einer aktuellen Phase-III-Studie vielversprechende Ergebnisse und könnte in Zukunft durch die Anwendung in oralen Kapseln eine unkomplizierte Alternative zur FMT darstellen. Toxoid-Impfstoff Die Hoffnungen auf einen gut wirksamen Toxoid-Impfstoff zur Primär- und Sekundärprävention von CDI haben sich in der CLOVER-Studie leider nicht erfüllt.

Purpose The aim of this study was to analyze the heart dose for left-sided breast cancer that can be achieved during daily practice in patients treated with multicatheter brachytherapy (MCBT) accelerated partial-breast irradiation (APBI) and deep-inspiration breath-hold (DIBH) whole-breast irradiation (WBI) using a simultaneous integrated tumor bed boost (SIB)—two different concepts which nonetheless share some patient overlap. Materials and methods We analyzed the nominal average dose (Dmean) to the heart as well as the biologically effective dose (BED) and the equivalent dose in 2‑Gy fractions (EQD2) for an α/β of 3 in 30 MCBT-APBI patients and 22 patients treated with DIBH plus SIB. For further dosimetric comparison, we contoured the breast planning target volume (PTV) in each of the brachytherapy planning CTs according to the ESTRO guidelines and computed tangential field plans. Mean dose (Dmean), EQD2 Dmean, and BED Dmean for three dosing schemes were calculated: 50 Gy/25 fractions and two hypofractionated regimens, i.e., 40.05 Gy/15 fractions and 26 Gy/5 fractions. Furthermore, we calculated tangential field plans without a boost for the 22 cases treated with SIB with the standard dosing scheme of 40.05 Gy/15 fractions. Results MCBT and DIBH radiation therapy both show low-dose exposure of the heart. As expected, hypofractionation leads to sparing of the heart dose. Although MCBT plans were not optimized regarding dose to the heart, Dmean differed significantly between MCBT and DIBH (1.28 Gy vs. 1.91 Gy, p p Conclusion In daily practice, both DIBH radiation therapy as well as MCBT show a very low heart exposure and may thus reduce long term cardiac morbidity as compared to currently available long-term clinical data of patients treated with conventional tangential field plans in free breathing. Our analysis confirms particularly good cardiac sparing with MCBT-APBI, so that this technique should be offered to patients with left-sided breast cancer if the tumor-associated eligibility criteria are fulfilled.

The COVID-19 pandemic and public life restrictions may have a negative impact on people's mental health. Therefore, we analyzed whether this condition affected the occurrence of suicide attempts (SA) over 20 months during the pandemic period.We included patient records according to DSM-5 criteria for suicidal behavior disorders (n = 825) between Jan 1, 2017, and Dec 31, 2021. We applied interrupted time-series Poisson regression models to investigate the effect of the pandemic on SA occurrence, time trends, and seasonal patterns in the whole group of patients as well as stratified by age and gender.There was no significant effect of the pandemic on the occurrence of SA in the overall group. However, we observed a significant impact of the pandemic on the seasonal pattern of SA, also the variance differed significantly (pre-pandemic mean ± variance: 13.33 ± 15.75, pandemic: mean ± variance: 13.86 ± 7.26), indicating less periodic variation in SA during the pandemic. Male patients and young adults mainly contributed to this overall effect. Subgroup analysis revealed a significant difference in SA trends during the pandemic in older adults (55 years) compared with younger adults (18-35 years); SA numbers increased in older adults and decreased in younger adults as the pandemic progressed.A few patients may have received initial care in an emergency department after SA without being referred to psychiatry.In general, the COVID-19 pandemic and related measures did not significantly affect the occurrence of SA but did significantly affect the dynamics. In addition, the pandemic appeared to affect suicidal behavior differently across age groups as it progressed. Particularly for the older adult group, negative long-term effects of the pandemic on suicidal behavior can be derived from the present results, indicating the need to strengthen suicide prevention for the elderly.

Understanding the genetic basis of human diseases and traits is dependent on the identification and accurate genotyping of genetic variants. Deep whole-genome sequencing (WGS), the gold standard technology for SNP and indel identification and genotyping, remains very expensive for most large studies. Here, we quantify the extent to which array genotyping followed by genotype imputation can approximate WGS in studies of individuals of African, Hispanic/Latino, and European ancestry in the US and of Finnish ancestry in Finland (a population isolate). For each study, we performed genotype imputation by using the genetic variants present on the Illumina Core, OmniExpress, MEGA, and Omni 2.5M arrays with the 1000G, HRC, and TOPMed imputation reference panels. Using the Omni 2.5M array and the TOPMed panel, ≥90% of bi-allelic single-nucleotide variants (SNVs) are well imputed (r(2) > 0.8) down to minor-allele frequencies (MAFs) of 0.14% in African, 0.11% in Hispanic/Latino, 0.35% in European, and 0.85% in Finnish ancestries. There was little difference in TOPMed-based imputation quality among the arrays with >700k variants. Individual-level imputation quality varied widely between and within the three US studies. Imputation quality also varied across genomic regions, producing regions where even common (MAF > 5%) variants were consistently not well imputed across ancestries. The extent to which array genotyping and imputation can approximate WGS therefore depends on reference panel, genotype array, sample ancestry, and genomic location. Imputation quality by variant or genomic region can be queried with our new tool, RsqBrowser, now deployed on the Michigan Imputation Server.

Heme (Fe2+-protoporphyrin IX) is a well-known protein prosthetic group; however, heme and hemin (Fe3+-protoporphyrin IX) are also increasingly viewed as signaling molecules. Among the signaling targets are numerous ion channels, with intracellular-facing heme-binding sites modulated by heme and hemin in the sub-µM range. Much less is known about extracellular hemin, which is expected to be more abundant, in particular after hemolytic insults. Here we show that the human cardiac voltage-gated sodium channel hNaV1.5 is potently inhibited by extracellular hemin (IC 50 ≈ 80 nM), while heme, dimethylhemin, and protoporphyrin IX are ineffective. Hemin is selective for hNaV1.5 channels: hNaV1.2, hNaV1.4, hNaV1.7, and hNaV1.8 are insensitive to 1 µM hemin. Using domain chimeras of hNaV1.5 and rat rNaV1.2, domain II was identified as the critical determinant. Mutation N803G in the domain II S3/S4 linker largely diminished the impact of hemin on the cardiac channel. This profile is reminiscent of the interaction of some peptide voltage-sensor toxins with NaV channels. In line with a mechanism of select gating modifiers, the impact of hemin on NaV1.5 channels is reversely use dependent, compatible with an interaction of hemin and the voltage sensor of domain II. Extracellular hemin thus has potential to modulate the cardiac function.

The aim of this study was to determine the effects of silver nanoparticles (AgNPs; speciation: NM-300 K) in the lab on the behavior of larvae in European Whitefish (iCoregonus lavaretus/i), a relevant model species for temperate aquatic environments during alternating light and darkness phases. The behavioral parameters measured included activity, turning rate, and distance moved.iC. lavaretus/iwere exposed to AgNP at nominal concentrations of 0, 5, 15, 45, 135, or 405 µg/L (n = 33, each) and behavior was recorded using a custom-built tracking system equipped with light sources that reliably simulate light and darkness. The observed behavior was analyzed using generalized linear mixed models, which enabled reliable detection of AgNP-related movement patterns at 10-fold higher sensitivity compared to recently reported standard toxicological studies. Exposure to 45 µg/L AgNPs significantly resulted in hyperactive response patterns for both activity and turning rates after an illumination change from light to darkness suggesting that exposure to this compound triggered escape mechanisms and disorientation-like behaviors iniC. lavaretus/ifish larvae. Even at 5 µg/L AgNPs some behavioral effects were detected, but further tests are required to assess their ecological relevance. Further, the behavior of fish larvae exposed to 135 µg/L AgNPs was comparable to the control for all test parameters, suggesting a triphasic dose response pattern. Data demonstrated the potential of combining generalized linear mixed models with behavioral investigations to detect adverse effects on aquatic species that might be overlooked using standard toxicological tests.

Background: Positive family history and genetic risk scores have been shown to independently capture those individuals with high risk for stroke. The aim of our study was to evaluate the amount of shared information between family history and genetic risk and to investigate their combined effect on the association with prevalent and incident stroke cases. Methods: We obtained a family risk score (FamRS), weighted for disease onset and family size as well as genome-wide polygenic risk score (PGS) including over 3.2 million single-nucleotide polymorphisms in the population-based prospective KORA F3 (Cooperative Health Research in the Region of Augsburg) study (n=3071) from Southern Germany. FamRS and PGS were evaluated separately and combined. The measures were once treated as continuous variables but also divided in the highest 20%, 10%, 5%, and 1% percentiles. Odds ratios via logistic regression and hazard ratios via Cox regression were estimated. A stroke event was defined as a hospitalization for stroke that was self-reported in a standardized interview by certified and supervised personnel. Results: The FamRS outperformed other simplified family measures such as affected parents or number of affected family members. FamRS and PGS were not correlated, and no individuals were observed with both very high FamRS and very high PGS (top 1% percentile). In a combined model, both FamRS and PGS were independently from each other associated with risk of stroke, also independent of other traditional risk factors (p [FamRS]=0.02, p [PGS]=0.005). Individuals in the top 1% of either FamRS or PGS were found to have >5-fold risk for stroke (odds ratios, 5.82 [95% CI, 2.08–14]; P =0.0002). The results for incident stroke events showed the same trend but were not significant. Conclusions: Our study shows that a family risk score and PGS capture different information concerning individual stroke risk. Combining the risk measures FamRS and PGS increases predictive power, as demonstrated in a population-based study.

Over the last decade, Haplogrep has become a standard tool for haplogroup classification in the field of human mitochondrial DNA and is widely used by medical, forensic, and evolutionary researchers. Haplogrep scales well for thousands of samples, supports many file formats and provides an intuitive graphical web interface. Nevertheless, the currently available version has limitations when applying it to large biobank-scale data. In this paper, we present a major upgrade to the software by adding (a) haplogroup summary statistics and variant annotations from various publicly available genome databases, (b) an interface to connect new phylogenetic trees, (c) a new state-of-the-art web framework managing large scale data, (d) algorithmic adaptions to improve FASTA classification using BWA-specific alignment rules and (e) a pre-classification quality control step for VCF samples. These improvements will give researchers the opportunity to classify thousands of samples as usual but providing additional ways to investigate the dataset directly in the browser. The web service and its documentation can be accessed freely without any registration at https://haplogrep.i-med.ac.at.

In spite of the existence of a variety of syntactic approaches, it is generally acknowledged that the verbal clauses are a central topic of the syntax. In contrast, verbless clauses which contain no verb element, and often also no subject, are not included in the prominent theoretical approaches to the syntax. Although there are many similarities between both these categories of clauses, there are also many differences, especially with respect to the way they are usually treated. Verbless clauses are mostly described as a reduction of finite clauses or an exception to the syntactic structures. This paper is offered as a contribution to the long-standing discussion related to the grammatical status and usage of the constructions without a finite verb. A corpus-based analysis of these constructions shows that the verbless clauses tend to occur in various forms and contexts. Moreover, the results of this study suggest that in many cases verbless clauses are able to fulfill specific communicative functions, which cannot be expressed by any other syntactic units, including finite clauses.

Genotype imputation is an integral tool in genome-wide association studies, in which it facilitates meta-analysis, increases power, and enables fine-mapping. With the increasing availability of whole-genome-sequence datasets, investigators have access to a multitude of reference-panel choices for genotype imputation. In principle, combining all sequenced whole genomes into a single large panel would provide the best imputation performance, but this is often cumbersome or impossible due to privacy restrictions. Here, we describe meta-imputation, a method that allows imputation results generated using different reference panels to be combined into a consensus imputed dataset. Our meta-imputation method requires small changes to the output of existing imputation tools to produce necessary inputs, which are then combined using dynamically estimated weights that are tailored to each individual and genome segment. In the scenarios we examined, the method consistently outperforms imputation using a single reference panel and achieves accuracy comparable to imputation using a combined reference panel.

The detection of contamination is key in all types of sequencing studies, especially for mitochondrial (mtDNA) studies. Contamination can lead to genotype misclassification and ultimately false-positive associations. In mtDNA studies, contamination is usually detected by applying computational expensive approaches using nuclear DNA (nDNA) reads. Here, we describe a novel approach that relies on the unique properties of the small mitochondrial genome to detect contamination fast and accurately.

Background and aims: High lipoprotein(a) [Lp(a)] concentrations are associated with increased coronary artery disease (CAD) risk. Lp(a) is regulated mainly genetically by the LPA gene but involved genetic variants have not been fully elucidated. Improved understanding of the entanglements of genetic Lp(a) regulation may enhance genetic prediction of Lp(a) and CAD risk. We investigated an interaction between the well-known LPA missense SNP rs41272110 (known as Thr3888Pro) and the frequent LPA splicing mutation KIV-2 4925G>A. Methods: Effects on Lp(a) concentrations were investigated by multiple quantile regression in the German Chronic Kidney Disease (GCKD) study, KORA-F3 and KORA-F4 (ntotal = 10,405) as well as in the UK Biobank (UKB) 200k exome dataset (n = 173,878). The impact of the interaction on CAD risk was assessed by survival analysis in UKB. Results: We observed a significant SNP-SNP interaction in all studies (p = 1.26e-05 to 3.03e-04). In quantile regression analysis, rs41272110 as a predictor shows no impact on Lp(a) (β = −0.06 [-0.79; 0.68], p = 0.879), but in a joint model including both SNPs as predictors, rs41272110 is associated with markedly higher Lp(a) (β = +9.40 mg/dL [6.45; 12.34], p = 4.07e-10). Similarly, rs41272110 shows no effect on CAD in UKB (HR = 1.01 [0.97; 1.04], p = 0.731), while rs41272110 carriers not carrying 4925G>A show an increased CAD risk (HR = 1.10 [1.04; 1.16], p = 6.9e-04). This group corresponds to 4% of the population. Adjustment for apolipoprotein(a) isoforms further modified the effect estimates markedly. Conclusions: This work emphasizes the complexity of the genetic regulation of Lp(a) and the importance to account for genetic subgroups in Lp(a) association studies and when interpreting genetic cardiovascular risk profiles.

A new family of hybrid/mixed finite elements optimized for numerical stability is introduced. It comprises a linear hexahedral and quadratic hexahedral and tetrahedral elements. The element formulation is derived from a consistent linearization of a well-known three-field functional and related to Simo–Taylor–Pister () elements. For the quadratic hexahedral and tetrahedral elements we derive (static reduced) discontinuous hybrid elements, as well as continuous mixed finite elements with additional primary unknowns for the hydrostatic pressure and the dilation, whereas the linear hexahedral element is of the discontinuous type. The elements can readily be used in combination with any isotropic, invariant-based hyperelastic material model and can be considered as being locking-free. In a representative numerical benchmark test the elements numerical stability is assessed and compared to -elements and the family of discontinuous hybrid elements implemented in the commercial finite element code Abaqus/Standard. The new elements show a significant advantage concerning the numerical robustness.

Zusammenfassung Hintergrund Die Depression ist neben kognitiven, emotionalen, sozialen und psychomotorischen Beeinträchtigungen durch spezifische stimmliche Merkmale gekennzeichnet. Bisher existieren erst wenige Studien, die diese in klinischen Kontexten und in Abgrenzung zu Gesunden untersuchten. Fragestellung Untersucht wurde der Zusammenhang zwischen Depressivität und paraverbalen Merkmalen bei depressiven Patient_innen und gesunden Probanden. Methode In einem mehrschrittigen Verfahren wurden die Audioinhalte von Anamneseinterviews mit Depressiven (n = 15) und Gesunden (n = 15) mit einer Software annotiert und transkribiert. Die paraverbalen Merkmale Grundfrequenz der Stimme, Spannweite der Stimme, Sprechgeschwindigkeit und Pausenlänge wurden automatisiert bestimmt. Mithilfe hierarchisch linearer Modelle wurde der Einfluss der Gruppenzugehörigkeit, Depressivität, Ängstlichkeit sowie psychischer und körperlicher Gesundheit auf die paraverbalen Merkmale analysiert. Ergebnisse Es zeigte sich ein Zusammenhang zwischen Depressivität und der Sprechgeschwindigkeit. Zwischen der Spannweite der Grundfrequenz, der Pausenlänge und Depressivität konnten tendenzielle Zusammenhänge gefunden werden. Depressive Patient_innen sind im Vergleich zu Gesunden durch eine monotone Sprache, eine geringe Sprechgeschwindigkeit und längere Pausen gekennzeichnet. Sprechgeschwindigkeit und Pausenlänge waren ebenfalls mit Ängstlichkeit assoziiert. Diskussion Sprechgeschwindigkeit, Pausenlänge und Spannweite der Grundfrequenz scheinen relevante Indikatoren für Depressivität/ggf. Ängstlichkeit zu sein. Die Spannweite der Grundfrequenz ist eher depressionsspezifisch, während Pausenlänge und Sprechgeschwindigkeit mit Depressivität und Ängstlichkeit assoziiert sind. Zukünftige Studien sollten die Zusammenhänge in größeren Stichproben verschiedener klinischer Störungsbilder untersuchen.

The non-fluorescent 9-nitrobenzo[b]quinolizinium is readily reduced by nitroreductase to a fluorescent reaction product. The resulting light-up effect enables the selective detection of nitro-reductase activity in vitro and in Escherichia coli bacterial cultures.

Supplementary Figure Legend from Appearance of the Novel Activating F1174S ALK Mutation in Neuroblastoma Correlates with Aggressive Tumor Progression and Unresponsiveness to Therapy

In cellulocrystallization is a rarely occurring event in nature. Recent advances, making use of heterologous overexpression, can promote the intracellular formation of protein crystals, but new tools are required to detect and to characterize these targets in the complex cell environment. In the present work we make use of Mask R-CNN, a Convolutional Neural Network (CNN) based instance segmentation method, for the identification of either single or multi-shaped crystals growing in living insect cells, using conventional bright field images. The algorithm can be rapidly adapted to recognize different targets, with the aim to extract relevant information to support a semi-automated screening pipeline, with the purpose to aid in the development of the intracellular protein crystallization approach.

Background Colon conduit is an alternative approach to reconstructing the alimentary tract after esophagectomy. Hyperspectral imaging (HSI) has been demonstrated to be effective for evaluating the perfusion of gastric conduits, but not colon conduits. This is the first study to describe this new tool addressing image-guided surgery and supporting esophageal surgeons to select the optimal colon segment for the conduit and anastomotic site intraoperatively. Patients and methods Of 10 patients, eight who underwent reconstruction with a long-segment colon conduit after esophagectomy between 01/05/2018 and 01/04/2022 were included in this study. HSI was recorded at the root and tip of the colon conduit after clamping the middle colic vessels, allowing us to evaluate the perfusion and appropriate part of the colon segment. Results Anastomotic leak (AL) was detected in only one (12.5%) of all the enrolled patients (n = 8). None of the patients developed conduit necrosis. Only one patient required re-anastomosis on postoperative day 4. No patient needed conduit removal, esophageal diversion, or stent placement. There was a change in the anastomosis site to proximal in two patients intraoperatively. There was no need to change the side of colon conduit intraoperatively in any patient. Conclusion HSI is a promising and novel intraoperative imaging tool to objectively assess the perfusion of the colon conduit. It helps the surgeon to define the best perfused anastomosis site and the side of colon conduit in this type of operation.

Streams of event weights in particle-level Monte Carlo event generators are a convenient and immensely CPU-efficient approach to express systematic uncertainties in phenomenology calculations, providing systematic variations on the nominal prediction within a single event sample. But the lack of a common standard for labelling these variation streams across different tools has proven to be a major limitation for event-processing tools and analysers alike. Here we propose a well-defined, extensible community standard for the naming, ordering, and interpretation of weight streams that will serve as the basis for semantically correct parsing and combination of such variations in both theoretical and experimental studies., 11 pages

Supplemental material, sj-pdf-1-jht-10.1177_10963480231171330 for Tourism Actors’ Responsible Behavior: A Systematic Literature Review by Sarah Schönherr in Journal of Hospitality & Tourism Research

Supplemental material, sj-pdf-1-jht-10.1177_10963480231171330 for Tourism Actors’ Responsible Behavior: A Systematic Literature Review by Sarah Schönherr in Journal of Hospitality & Tourism Research

Polymer brushes with tailored surface functionalities are important materials to manipulate the interactions between cells and surfaces in a biomedical context. To enhance the control of the conjugation of cell-adhesive peptides to the polymer brush terminus, poly(di(ethylene glycol)methyl ether methacrylate) (PDEGMA) brushes were fabricated via interface-mediated reversible addition-fragmentation chain transfer (RAFT) polymerization on titanium substrates. Due to the immobilization of 4-((((2-carboxyethyl)thio)carbonothioyl)thio)-4-cyanopentanoic acid as a chain transfer agent (CTA) on the titanium substrates before the subsequent RAFT polymerization, terminal carboxylic acid groups were introduced in the brushes. The brushes obtained were characterized by ellipsometry, static water contact angle measurements, X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared (FT-IR) spectroscopy. PDEGMA brushes allow the facile conjugation of peptides containing the arginine-glycine-aspartic acid (GRGDS) sequence, which afforded the peptide-specific attachment of NIH 3T3 fibroblasts. By contrast, the inhibition of cell attachment was observed on PDEGMA brushes with 7 nm dry thickness conjugated with arginine-alanine-aspartic acid (GRADS). The strategy of surface functional group modification with controllable antifouling or cell-adhesive properties will allow a versatile bio-functionalization approach independent of the underlying surface condition as polymeric biomaterials, among others, in titanium-based medical implant devices.

Background Comorbidities including ischemic heart disease (IHD) worsen outcomes after SARS‐CoV‐2 infections. High lipoprotein(a) [Lp(a)] concentrations are a strong risk factor for IHD and possibly for thromboembolic events. We therefore evaluated whether SARS‐CoV‐2 infections modify the risk of high Lp(a) concentrations for IHD or thromboembolic events during the first 8.5 months follow‐up of the pandemic. Method Cohort study using data from the UK Biobank during the SARS‐CoV‐2 pandemic. Baseline Lp(a) was compared between SARS‐CoV‐2 positive patients and the population controls. UK Biobank received ethical approval from the North West Multi‐Centre Research Ethics Committee (REC reference: 11/NW/0382). All participants gave written informed consent before enrolment in the study, which was conducted in accordance with the principles of the Declaration of Helsinki. Results SARS‐CoV‐2 positive patients had Lp(a) concentrations similar to the population controls. The risk for IHD increased with higher Lp(a) concentrations in both, the population controls (n = 435,104) and SARS‐CoV‐2 positive patients (n = 6,937). The causality of the findings was supported by a genetic risk score for Lp(a). A SARS‐CoV‐2 infection modified the association with a steeper increase in risk for infected patients (interaction P‐value = 0.03). Although SARS‐CoV‐2 positive patients had a 5‐times higher frequency of thromboembolic events compared to the population controls (1.53% vs. 0.31%), the risk was not influenced by Lp(a). Conclusions SARS‐CoV‐2 infections enforce the association between high Lp(a) and IHD but the risk for thromboembolic events is not influenced by Lp(a). This article is protected by copyright. All rights reserved

Cell sheet harvesting offers a great potential for the development of new therapies for regenerative medicine. For cells to adhere onto surfaces, proliferate, and to be released on demand, thermoresponsive polymeric coatings are generally considered to be required. Herein, an alternative approach for the cell sheet harvesting and rapid release on demand is reported, circumventing the use of thermoresponsive materials. This approach is based on the end-group biofunctionalization of non-thermoresponsive and antifouling poly(2-hydroxyethyl methacrylate) (p(HEMA)) brushes with cell-adhesive peptide motifs. While the non-functionalized p(HEMA) surfaces are cell-repellant, ligation of cell-signaling ligand enables extensive attachment and proliferation of NIH 3T3 fibroblasts until the formation of a confluent cell layer. Remarkably, the formed cell sheets can be released from the surfaces by gentle rinsing with cell-culture medium. The release of the cells is found to be facilitated by low surface density of cell-adhesive peptides, as confirmed by X-ray photoelectron spectroscopy (XPS). Additionally, the developed system affords possibility for repeated cell seeding, proliferation and release on previously used substrates without any additional pretreatment steps. This new approach represents an alternative to thermally triggered cell-sheet harvesting platforms offering possibility of capture and proliferation of various rare cell lines via appropriate selection the cell-adhesive ligand. This article is protected by copyright. All rights reserved.

Poor computing efficiency of precision event generators for LHC physics has become a bottleneck for Monte-Carlo event simulation campaigns. We provide solutions to this problem by focusing on two major components of general-purpose event generators: The PDF evaluator and the matrix-element generator. For a typical production setup in the ATLAS experiment, we show that the two can consume about 80% of the total runtime. Using NLO simulations of $pp\to\ell^+\ell^-+\text{jets}$ and $pp\to t\bar{t}+\text{jets}$ as an example, we demonstrate that the computing footprint of LHAPDF and Sherpa can be reduced by factors of order 10, while maintaining the formal accuracy of the event sample. The improved codes are made publicly available., Comment: 21 pages, 7 figures, 1 table, 2 listings

The fabrication, characterization and application of a nanoporous Silicon Rugate Filter (pSiRF) loaded with an enzymatically degradable polymer is reported as a bare eye detection optical sensor for enzymes of pathogenic bacteria, which is devoid of any dyes. The nanopores of pSiRF were filled with poly(lactic acid) (PLA), which, upon enzymatic degradation, resulted in a change in the effective refractive index of the pSiRF film, leading to a readily discernible color change of the sensor. The shifts in the characteristic fringe patterns before and after the enzymatic reaction were analyzed quantitatively by Reflectometric Interference Spectroscopy (RIfS) to estimate the apparent kinetics and its dependence on enzyme concentration. A clear color change from green to blue was observed by the bare eye after PLA degradation by proteinase K. Moreover, the color change was further confirmed in measurements in bacterial suspensions of the pathogen

ZusammenfassungIn seiner Arbeit als Paartherapeut mit meist heterosexuellen Paaren unterschiedlicher Altersgruppen wird der Autor immer wieder mit sexuellen Problemen konfrontiert. Oft geht es dabei um die geringere Lust oder Unlust der einen Seite und den damit verbundenen Frust auf der anderen Seite. Um nicht in einer unglücklichen Dynamik von Erwartung und Zurückweisung stecken zu bleiben und neue Türen zu öffnen, plädiert der Autor für eine neue Wertschätzung der Selbstbefriedigung.

We consider the production of a pair of $Z$ bosons at the LHC and study the inclusion of EW corrections in theoretical predictions at fixed order and based on multijet-merged parton-shower simulations. To this end we present exact NLO EW results for $pp\to e^+e^-\mu^+\mu^-$, and, for the first time, for $pp\to e^+e^-\mu^+\mu^-j$, and compare them to the EW virtual and NLL Sudakov approximation. We then match the exact NLO EW result to the resummed Sudakov logarithms to achieve an improved NLO EW + NLL $\text{EW}_\text{sud}^\text{exp}$ result. Further, we discuss the inclusion of the above EW corrections in MEPS@NLO event simulations in the framework of the Sherpa event generator. We present detailed phenomenological predictions for inclusive $ZZ$ and $ZZj$ production taking into account the dominant EW corrections through the EW virtual approximation, as well as through (exponentiated) EW Sudakov logarithms., Comment: 39 pages, 12 figures, 3 tables

The new German Radiation Protection Act (StrlSchG) of 31 December 2018 established a reference value of 300 Bq m−3 for the annual average radon activity concentration in buildings with recreation and living rooms, as well as in workplaces. It is expected that the reference value will be exceeded in a vast number of buildings throughout Germany and that radon protection measures will become indispensable. A simple and inexpensive radon protection measure for existing buildings is ventilation. In the scope of a joint project, ventilation systems with zone control and heat recovery are to be extended by the control parameter radon activity concentration. A highly sensitive, miniaturized radon monitor will be developed for this purpose, which can be integrated wirelessly into ventilation systems. Radon measurements were carried out in 13 apartments of an unoccupied heated apartment block in Germany over a period of three weeks in the wintertime. High radon activity concentrations were found on all three floors. The maximum values were 14000 Bq m−3 on the first floor, 6000 Bq m−3 on the second floor, and 2000 Bq m−3 on the third floor. Ventilation experiments were carried out in an apartment with high radon activity concentration. Two decentralized ventilation systems with heat recovery were installed in each of the two opposite outside walls. The controlling device of the system was activated wirelessly depending on the radon activity concentration. The radon activity concentration was reduced from 8000 Bq m−3 to 800 Bq m−3 in a first experiment in the living room.

Current treatment of chronic wounds has been critically limited by various factors, including bacterial infection, biofilm formation, impaired angiogenesis, and prolonged inflammation. Addressing these challenges, we developed a multifunctional wound dressing-based three-pronged approach for accelerating wound healing. The multifunctional wound dressing, composed of nanofibers, functional nanoparticles, natural biopolymers, and selected protein and peptide, can target multiple endogenous repair mechanisms and represents a promising alternative to current wound healing products.

The human leukocyte antigen (HLA) locus is associated with more human complex diseases than any other locus. In many diseases it explains more heritability than all other known loci combined. Investigators have now demonstrated the accuracy of in silico HLA imputation methods. These approaches enable rapid and accurate estimation of HLA alleles in the millions of individuals that are already genotyped on microarrays. HLA imputation has been used to define causal variation in autoimmune diseases, such as type I diabetes, and infectious diseases, such as HIV infection control. However, there are few guidelines on performing HLA imputation, association testing, and fine-mapping. Here, we present comprehensive statistical genetics guide to impute HLA alleles from genotype data. We provide detailed protocols, including standard quality control measures for input genotyping data and describe options to impute HLA alleles and amino acids including a web-based Michigan Imputation Server. We updated the HLA imputation reference panel representing global populations (African, East Asian, European and Latino) available at the Michigan Imputation Server (n = 20,349) and achived high imputation accuracy (mean dosage correlation r = 0.981). We finally offer best practice recommendations to conduct association tests in order to define the alleles, amino acids, and haplotypes affecting human traits. This protocol will be broadly applicable to the large-scale genotyping data and contribute to defining the role of HLA in human diseases across global populations.