Complete genome sequence of the linezolid-resistant clinical Enterococcus faecalis N23-3408 linked to a livestock lineage in Switzerland.

Here, we report the complete genome of human clinical linezolid-resistant Enterococcus faecalis N23-3408. N23-3408 harbored a 59.5 kb plasmid with antimicrobial resistance genes cat, erm(B), fexA, optrA, tet(L), and tet(M). Closely related E. faecalis harboring this plasmid was previously obtained from livestock animals and pet food in Switzerland.

State of Research on German Retirement Migration to Turkiye: A Qualitative Systematic Review.

Background: The Alanya region on Turkey's southern coast has become an important destination for German retirement migration. Objective: Identify research studies on German retirement migration to Turkey which deal with the life situation, the motives, the handling of critical life situations in the context of retirement migration, and the reasons for return migration. Methods: The researcher conducted a qualitative systematic literature review from January 2021 to May 2021 in MEDLINE, CINAHL Complete, and APA PsychInfo. Results: Eleven studies on German and European retirement migration to Turkey were included after a critical assessment based on defined inclusion and exclusion criteria. Motives for retirement migration are climatic, scenic, cultural advantages and the lower cost of living in Turkey. Conclusion: It has been found that most of the studies are thematically narrowly defined, detailed studies deal with and describe the development of retirement migration in a more general way.

BTK inhibition limits microglia-perpetuated CNS inflammation and promotes myelin repair.

In multiple sclerosis (MS), persisting disability can occur independent of relapse activity or development of new central nervous system (CNS) inflammatory lesions, termed chronic progression. This process occurs early and it is mostly driven by cells within the CNS. One promising strategy to control progression of MS is the inhibition of the enzyme Bruton's tyrosine kinase (BTK), which is centrally involved in the activation of both B cells and myeloid cells, such as macrophages and microglia. The benefit of BTK inhibition by evobrutinib was shown as we observed reduced pro-inflammatory activation of microglia when treating chronic experimental autoimmune encephalomyelitis (EAE) or following the adoptive transfer of activated T cells. Additionally, in a model of toxic demyelination, evobrutinib-mediated BTK inhibition promoted the clearance of myelin debris by microglia, leading to an accelerated remyelination. These findings highlight that BTK inhibition has the potential to counteract underlying chronic progression of MS.

Differentiating patients admitted primarily due to coronavirus disease 2019 (COVID-19) from those admitted with incidentally detected severe acute respiratory syndrome corona-virus type 2 (SARS-CoV-2) at hospital admission: A cohort analysis of German hospital records.

OBJECTIVE: The number of hospitalized patients with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) does not differentiate between patients admitted due to coronavirus disease 2019 (COVID-19) (ie, primary cases) and incidental SARS-CoV-2 infection (ie, incidental cases). We developed an adaptable method to distinguish primary cases from incidental cases upon hospital admission. DESIGN: Retrospective cohort study. SETTING: Data were obtained from 3 German tertiary-care hospitals. PATIENTS: The study included patients of all ages who tested positive for SARS-CoV-2 by a standard quantitative reverse-transcription polymerase chain reaction (RT-PCR) assay upon admission between January and June 2022. METHODS: We present 2 distinct models: (1) a point-of-care model that can be used shortly after admission based on a limited range of parameters and (2) a more extended point-of-care model based on parameters that are available within the first 24-48 hours after admission. We used regression and tree-based classification models with internal and external validation. RESULTS: In total, 1,150 patients were included (mean age, 49.5±28.5 years; 46% female; 40% primary cases). Both point-of-care models showed good discrimination with area under the curve (AUC) values of 0.80 and 0.87, respectively. As main predictors, we used admission diagnosis codes (ICD-10-GM), ward of admission, and for the extended model, we included viral load, need for oxygen, leucocyte count, and C-reactive protein. CONCLUSIONS: We propose 2 predictive algorithms based on routine clinical data that differentiate primary COVID-19 from incidental SARS-CoV-2 infection. These algorithms can provide a precise surveillance tool that can contribute to pandemic preparedness. They can easily be modified to be used in future pandemic, epidemic, and endemic situations all over the world.

Calf circumference as a surrogate indicator for detecting low muscle mass in hospitalized geriatric patients.

BACKGROUND: Sarcopenia is characterized by low muscle strength, decreased muscle mass, and decline in physical performance. While the measurements of muscle strength and physical performance are easy to perform, an accurate evaluation of muscle mass is technically more demanding. We therefore evaluated the suitability of calf circumference (CC) as a clinical indicator for muscle mass. METHODS: In a cross-sectional single-centre study, geriatric inpatients were assessed for sarcopenia according to the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) consensus. Calf circumference was tested for correlation with appendicular skeletal muscle mass index (ASMI). Receiver operating characteristic curves (ROC) were used to calculate the discriminatory value of the CC cut-off values to differentiate patients above and below ASMI cut-offs for sarcopenia. RESULTS: In this study population (n = 305, age 83.5 ± 7.0 years, BMI 25.7 kg/m2, 65.6% female), the prevalence of sarcopenia was 22.6%. In subjects with low ASMI, mean CC was 29.5 ± 3.4 cm for females and 32.0 ± 3.4 cm for males. A positive relationship between CC and ASMI was found. The optimized cut-off value for CC to identify patients with low ASMI was <31.5 cm for females (sensitivity 78%, specificity 79%), and <33.5 cm for males (sensitivity 71%, specificity 62%). CONCLUSION: In clinical settings where imaging technology for muscle mass quantification is not available, simple calf circumference measurement may be used as a dependable indicator for low muscle mass in older adults.

Deep Learning-Based Automated Labeling of Coronary Segments for Structured Reporting of Coronary Computed Tomography Angiography in Accordance With Society of Cardiovascular Computed Tomography Guidelines.

PURPOSE: To evaluate a novel deep learning (DL)-based automated coronary labeling approach for structured reporting of coronary artery disease according to the guidelines of the Society of Cardiovascular Computed Tomography (CT) on coronary CT angiography (CCTA). PATIENTS AND METHODS: A retrospective cohort of 104 patients (60.3 ± 10.7 y, 61% males) who had undergone prospectively electrocardiogram-synchronized CCTA were included. Coronary centerlines were automatically extracted, labeled, and validated by 2 expert readers according to Society of Cardiovascular CT guidelines. The DL algorithm was trained on 706 radiologist-annotated cases for the task of automatically labeling coronary artery centerlines. The architecture leverages tree-structured long short-term memory recurrent neural networks to capture the full topological information of the coronary trees by using a two-step approach: a bottom-up encoding step, followed by a top-down decoding step. The first module encodes each sub-tree into fixed-sized vector representations. The decoding module then selectively attends to the aggregated global context to perform the local assignation of labels. To assess the performance of the software, percentage overlap was calculated between the labels of the algorithm and the expert readers. RESULTS: A total number of 1491 segments were identified. The artificial intelligence-based software approach yielded an average overlap of 94.4% compared with the expert readers' labels ranging from 87.1% for the posterior descending artery of the right coronary artery to 100% for the proximal segment of the right coronary artery. The average computational time was 0.5 seconds per case. The interreader overlap was 96.6%. CONCLUSIONS: The presented fully automated DL-based coronary artery labeling algorithm provides fast and precise labeling of the coronary artery segments bearing the potential to improve automated structured reporting for CCTA.

Disturbed endothelial cell signaling in tumor progression and therapy resistance.

Growth of new blood vessels is considered requisite to cancer progression. Recent findings revealed that in addition to inducing angiogenesis, tumor-derived factors alter endothelial cell gene transcription within the tumor mass but also systemically throughout the body. This subsequently contributes to immunosuppression, altered metabolism, therapy resistance and metastasis. Clinical studies demonstrated that targeting the endothelium can increase the success rate of immunotherapy. Single-cell technologies revealed remarkable organ-specific endothelial heterogeneity that becomes altered by the presence of a tumor. In metastases, endothelial transcription differs remarkably between newly formed and co-opted vessels which may provide a basis for developing new therapies to target endothelial cells and overcome therapy resistance more effectively. This review addresses how cancers impact the endothelium to facilitate tumor progression.

Humoral and cellular immune responses in fully vaccinated individuals with or without SARS-CoV-2 breakthrough infection: Results from the CoV-ADAPT cohort.

Despite recent advances in prophylactic vaccination, SARS-CoV-2 infections continue to cause significant morbidity. A better understanding of immune response differences between vaccinated individuals with and without later SARS-CoV-2 breakthrough infection is urgently needed. CoV-ADAPT is a prospective long-term study comparing humoral (anti-spike-RBD-IgG, neutralization capacity, avidity) and cellular (spike-induced T-cell interferon-γ [IFN-γ] release) immune responses in individuals vaccinated against SARS-CoV-2 at four different time points (three before and one after third vaccination). In this cohort study, 62 fully vaccinated individuals presented with SARS-CoV-2 breakthrough infections vs 151 without infection 3-7 months following third vaccination. Breakthrough infections significantly increased anti-spike-RBD-IgG (p < 0.01), but not spike-directed T-cell IFN-γ release (TC) or antibody avidity. Despite comparable surrogate neutralization indices, the functional neutralization capacity against SARS-CoV-2-assessed via a tissue culture-based assay-was significantly higher following breakthrough vs no breakthrough infection. Anti-spike-RBD-IgG and antibody avidity decreased with age (p < 0.01) and females showed higher anti-spike-RBD-IgG (p < 0.01), and a tendency towards higher antibody avidity (p = 0.051). The association between humoral and cellular immune responses previously reported at various time points was lost in subjects after breakthrough infections (p = 0.807). Finally, a machine-learning approach based on our large immunological dataset (a total of 49 variables) from different time points was unable to predict breakthrough infections (area under the curve: 0.55). In conclusion, distinct differences in humoral vs cellular immune responses in fully vaccinated individuals with or without breakthrough infection could be demonstrated. Breakthrough infections predominantly drive the humoral response without boosting the cellular component. Breakthrough infections could not be predicted based on immunological data, which indicates a superior role of environmental factors (e.g., virus exposure) in individualized risk assessment.

Combined Biomarker System Predicts Prognosis in Patients with Metastatic Oral Squamous Cell Carcinoma.

BACKGROUND: Metastatic oral squamous cell carcinoma (OSCC) is associated with poor patient prognosis. Metastasis is a complex process involving various proteins, tumor cell alterations, including changes attributable to the epithelial-to-mesenchymal transition (EMT) process, and interactions with the tumor microenvironment (TME). In this study, we investigate a combined protein marker system consisting of connexin 43 (Cx43), EMMPRIN (CD147), E-cadherin, and vimentin, with a focus on their roles in the invasive metastatic progression of OSCC and their potential utility in predicting prognosis. METHODS: We conducted an immunohistochemical analysis to assess the protein expression profiles of Cx43, EMMPRIN, E-cadherin, and vimentin using tissue samples obtained from 24 OSCC patients. The metastatic process was mapped through different regions of interest (ROIs), including adjacent healthy oral mucosa (OM), center of primary OSCC, invasive front (IF), and local cervical lymph node metastases (LNM). The primary clinical endpoints were disease-free survival (DFS) and overall survival (OS). RESULTS: Substantial changes in the expression profiles of the different marker proteins were observed among the different ROIs, with all p-values < 0.05, signifying statistical significance. Multivariable Cox regression analysis results showed a significant effect of increased EMMPRIN expression toward the IF on DFS (p = 0.019) and OS (p = 0.023). Furthermore, the combined predictive analysis showed a significant predictive value of the marker system for DFS (p = 0.0017) and OS (p = 0.00044). CONCLUSIONS: The combined marker system exhibited a significant ability to predict patient prognosis. An increase in EMMPRIN expression toward the IF showed the strongest effect and could be an interesting new antimetastatic therapy approach.

24/7 Therapeutic Drug Monitoring of Beta-Lactam Antibiotics with CLAM-2000.

BACKGROUND: The aim of this study was to evaluate the CLAM-2000 automated preanalytical sample preparation module with integrated liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) as a method for 24/7 therapeutic drug monitoring (TDM) of beta-lactam antibiotics in routine clinical diagnostics. METHODS: Method validation was performed using quality control samples. Method comparison was performed with routine samples from patients treated with beta-lactam antibiotics. RESULTS: The determination of piperacillin, meropenem, ceftazidime, flucloxacillin, and cefotaxime was performed using D5-piperacillin and D6-meropenem as internal standards. The linearity of the method was within the therapeutic range of beta-lactam antibiotics. The imprecision and accuracy data obtained from quality control samples were within 15%, and the imprecision of patient samples on the instrument was less than the 5% coefficient of variation (CV). Internal standards stored in the instrument at 9 °C for at least one week were stable, which facilitated reagent use and storage. CONCLUSION: The CLAM-2000 (Shimadzu, Kyoto, Japan) provides reproducible results as an established routine instrument and is a useful tool for 24/7 TDM of beta-lactam antibiotics in routine clinical diagnostics.

Shadow-Imaging-Based Triangulation Approach for Tool Deflection Measurement.

As incrementally formed sheets show large geometric deviations resulting from the deflection of the forming tool, an in-process measurement of the tool tip position is required. In order to cover a measuring volume of 2.0 m × 1.0 m × 0.2 m and to achieve measuring uncertainties of less than 50 µm, a multi-sensor system based on triangulation is realized. Each shadow imaging sensor in the multi-sensor system evaluates the direction vector to an LED attached to the tool, and the three-dimensional position of the LED is then determined from the combination of two sensors. Experimental results show that the angle of view from the sensor to the LED limits both the measurement range and the measurement uncertainty. The measurement uncertainty is dominated by systematic deviations, but these can be compensated, so that the measurement uncertainty required for measuring the tool tip position in the ISF is achieved.

Non-targeted metabolomics aids in sex pheromone identification: a proof-of-concept study with the triangulate cobweb spider, Steatoda triangulosa.

Targeted metabolomics has been widely used in pheromone research but may miss pheromone components in study organisms that produce pheromones in trace amount and/or lack bio-detectors (e.g., antennae) to readily locate them in complex samples. Here, we used non-targeted metabolomics-together with high-performance liquid chromatography-mass spectrometry (HPLC-MS), gas chromatography-MS, and behavioral bioassays-to unravel the sex pheromone of the triangulate cobweb spider, Steatoda triangulosa. A ternary blend of three contact pheromone components [N-4-methylvaleroyl-O-isobutyroyl-L-serine (5), N-3-methylbutyryl-O-isobutyroyl-L-serine (11), and N-3-methylbutyryl-O-butyroyl-L-serine (12)] elicited courtship by S. triangulosa males as effectively as female web extract. Hydrolysis of 5, 11 and 12 at the ester bond gave rise to two mate-attractant pheromone components [butyric acid (7) and isobutyric acid (8)] which attracted S. triangulosa males as effectively as female webs. Pheromone components 11 and 12 are reported in spiders for the first time, and were discovered only through the use of non-targeted metabolomics and GC-MS. All compounds resemble pheromone components previously identified in widow spiders. Our study provides impetus to apply non-targeted metabolomics for pheromone research in a wide range of animal taxa.

[Scoring tool to identify patients at increased risk for drug-related problems: results of a point prevalence study at hospital admission]. / Scoring-Tool zu Identifizierung von Patienten mit erhöhtem Risiko für Arzneimittel-bezogene Probleme- Bericht einer Punkt-Prävalenzuntersuchung bei Aufnahme im Krankenhaus.

INTRODUCTION: Drug therapy is a high-risk process and requires special attention, especially at sectoral borders. Pharmaceutical services such as medication review are appropriate measures to identify drug-related problems and thus improve the safety of drug therapy. Risk-scoring tools have been described in the literature as helpful for prioritizing medication reviews for patients at high risk for drug-related problems. METHODS: In a multi-centre point prevalence study, we identified patients at increased risk for medication-related problems at hospital admission using the medication risk tool. In addition, the current level of implementation of pharmacy services was surveyed. RESULTS: A total of 11 (58%; 11/19) hospital pharmacies in Saxony participated in the point prevalence survey. The scoring tool identified 32% (279/875) of patients at increased risk for medication-related problems (Meris score >12 group) at admission. Thereby, the number of drugs in the Meris score >12 group was 10.6 (average; standard deviation 3.5; n=279), while in the Meris score ≤12 group it was only five drugs per patient (average 4.6; standard deviation 2.8; n=596). The age of patients in the Meris score >12 group averaged 75.9 ± 11 years, while the age of patients in the Meris score ≤12 group averaged 60.6 ± 17.9 years. DISCUSSION: Prioritization with the help of a risk-scoring tool is essential as pharmacy services in Saxon hospitals still need to be regularly established and in order to identify patients with an increased risk for drug-related problems at an early stage.

Widow spiders alter web architecture and attractiveness in response to same-sex competition for prey and mates, and predation risk.

Female-female competition in animals has rarely been studied. Responses of females that compete context-dependently for mates and prey, and seek safety from predators, are ideally studied with web-building spiders. Cobwebs possess unique sections for prey capture and safety, which can be quantified. We worked with Steaoda grossa females because their pheromone is known, and adjustments in response to mate competition could be measured. Females exposed to synthetic sex pheromone adjusted their webs, indicating a perception of intra-sexual competition via their sex pheromone. When females sequentially built their webs in settings of low and high intra-sexual competition, they adjusted their webs to increase prey capture and lower predation risk. In settings with strong mate competition, females deposited more contact pheromone components on their webs and accelerated their breakdown to mate-attractant pheromone components, essentially increasing their webs' attractiveness. We show that females respond to sexual, social and natural selection pressures originating from intra-sexual competition.

Endothelial Notch1 signaling in white adipose tissue promotes cancer cachexia.

Cachexia is a major cause of morbidity and mortality in individuals with cancer and is characterized by weight loss due to adipose and muscle tissue wasting. Hallmarks of white adipose tissue (WAT) remodeling, which often precedes weight loss, are impaired lipid storage, inflammation and eventually fibrosis. Tissue wasting occurs in response to tumor-secreted factors. Considering that the continuous endothelium in WAT is the first line of contact with circulating factors, we postulated whether the endothelium itself may orchestrate tissue remodeling. Here, we show using human and mouse cancer models that during precachexia, tumors overactivate Notch1 signaling in distant WAT endothelium. Sustained endothelial Notch1 signaling induces a WAT wasting phenotype in male mice through excessive retinoic acid production. Pharmacological blockade of retinoic acid signaling was sufficient to inhibit WAT wasting in a mouse cancer cachexia model. This demonstrates that cancer manipulates the endothelium at distant sites to mediate WAT wasting by altering angiocrine signals.

Capabilities and limits of surface roughness measurements with monochromatic speckles.

For coherent light illumination, surface roughness leads to speckles in the scattered light image. By evaluating the speckle contrast or image auto-correlation, a measurement of the roughness parameter S q is possible. While these measurement principles have been well known for decades, a fundamental understanding of the minimal achievable measurement uncertainty is missing. Therefore, the measurement uncertainty limits for four unavoidable sources of uncertainty are derived by means of theoretical and numerical approaches. The study is focused on the case of monochromatic speckles, which provide the highest sensitivity, as well as on the case of planar surface and isotropic surface roughness with a Gaussian height distribution and Gaussian correlation function. The considered uncertainty sources are the natural randomness of surface roughness itself, speckle noise, quantum shot noise, and camera noise. As a result, for the studied experimental configuration, speckle noise is determined as the largest contribution to measurement uncertainty, which leads to a minimal achievable relative uncertainty of 1%-2% for S q =(0.03-0.15)λ. According to theoretical studies, the speckle noise limit of the relative uncertainty is inversely proportional to four times the square root of the independent number of evaluated speckles. In addition, an absolute uncertainty limit is reached for ever-smoother surfaces, which amounts to λ divided by 64 times the square root of the independent number of evaluated speckles. Furthermore, systematic errors due to cross-sensitivity with respect to other parameters of surface roughness (height distribution, correlation length) as well as the surface position and shape (axial offset, tilt, curvature) are quantified and discussed. For the considered small deviations of different influencing quantities, the quantified errors are one order of magnitude smaller than the speckle noise limit.

Retroperitoneoscopic adrenalectomy may be superior to laparoscopic transperitoneal adrenalectomy in terms of costs and profit: a retrospective pair-matched cohort analysis.

BACKGROUND: A direct comparison of the cost-benefit analysis of retroperitoneoscopic adrenalectomy (RPA) versus the minimally invasive transperitoneal access (LTA) approach is currently lacking. We hypothesized that RPA is more cost effective than LTA; promising significant savings for the healthcare system in an era of ever more limited resources. METHODS: We performed a monocentric retrospective observational cohort study based on data from our Endocrine Surgery Registry. Patients who were operated upon between 2019 and 2022 were included. After pair-matching, both cohorts (RPA vs. LTA) were compared for perioperative variables and treatment costs (process cost calculation), revenue and profit. RESULTS: Two homogenous cohorts of 43 patients each (RPA vs. LTA) were identified following matching. Patient characteristics between the cohorts were comparable. In terms of both treatment-associated costs and profit, the RPA procedure was superior to LTA (costs: US$5789.99 for RPA vs. US$6617.75 for LTA, P = 0.043; profit: US$1235.59 for RPA vs. US$653.33 for LTA, P = 0.027). The duration of inpatient treatment and comorbidities significantly influenced the cost of treatment and the overall profit. CONCLUSIONS: RPA appears not only to offer benefits over LTA in terms of perioperative morbidity and length of hospital stay, but also has a superior financial cost/benefit profile.

L-Arginine sulfate reduces irreversible protein binding in immobilized metal affinity chromatography.

Immobilized metal affinity chromatography (IMAC) is a powerful technique for capture and purification of relevant biopharmaceuticals in complex biological matrices. However, protein recovery can be drastically compromised due to surface induced spreading and unfolding of the analyte, leading to fouling of the stationary phase. Here, we report on the kinetics of irreversible adsorption of a protease on an IMAC resin in a time span ranging from minutes to several hours. This trend correlated with the thermal data measured by nano differential scanning calorimetry, and showed a time-dependent change in protein unfolding temperature. Our results highlight that 'soft' proteins show a strong time dependent increase in irreversible adsorption. Furthermore, commonly used co-solvents for preservation of the native protein conformation are tested for their ability to reduce fouling. Thermal data suggests that the amino acid l-arginine is beneficial in preventing unfolding, which was confirmed in batch adsorption experiments. The choice of counter-ions has to be considered when using this amino acid. These results show that l-arginine sulfate decelerates the irreversible adsorption kinetics of proteins on the IMAC stationary phase to a greater extent than l-arginine chloride.

An inter-model comparison of parabolic equation methods for sound propagation from wind turbines.

The modeling of sound propagation for land-based wind turbines is a complex task that takes various parameters into account. Not only do the wind speed and wind direction affect the noise received at a certain position by changing the refraction of the sound, but also the terrain complexity, ground impedance, and receiver position relative to the source and ground all affect propagation. These effects are seen by the reflections of the sound at the ground surface causing interference of sound waves, or by the receiver being positioned in and out of noise shadow zones in the upwind far field position, or in steep terrain irregularities. Several sound propagation models with different levels of fidelity have been developed through time to account for these effects. This paper will focus on two different parabolic equation models, the Beilis-Tappert Parabolic Equation and the Generalized Terrain Parabolic Equation, through theoretical studies of varying terrain complexity, ground impedance, and sound speed profiles (upwind, downwind, and no wind). In addition, the propagation models are validated through spectral comparisons to noise measurements from two different campaigns considering loudspeaker noise and wind turbine noise, respectively.