Impaired Hemostatic and Immune Functions of Platelets After Acute Thrombocytopenia.

Background: Platelets are pivotal in maintaining vascular integrity, hemostasis, and immune modulation, with newly generated, immature platelets being the most responsive in fulfilling these tasks. Therefore, the immature platelet fraction provides insights into thrombopoiesis dynamics and clinical prognostication. However, it is currently unclear how immature platelet functions change in settings of acute thrombocytopenia.

USP10 drives cancer stemness and enables super-competitor signalling in colorectal cancer.

The contribution of deubiquitylating enzymes (DUBs) to β-Catenin stabilization in intestinal stem cells and colorectal cancer (CRC) is poorly understood. Here, and by using an unbiassed screen, we discovered that the DUB USP10 stabilizes β-Catenin specifically in APC-truncated CRC in vitro and in vivo. Mechanistic studies, including in vitro binding together with computational modelling, revealed that USP10 binding to β-Catenin is mediated via the unstructured N-terminus of USP10 and is outcompeted by intact APC, favouring β-catenin degradation.

Detection of Vancomycin Resistant Genes in Intrinsically Antibiotic Resistant Bacteria from the Gut Microbiota of Indonesian Individuals.

Background: Antibiotic resistance is a global public health concern that has been exacerbated by the overuse and misuse of antibiotics, leading to the emergence of resistant bacteria. The gut microbiota, often influenced by antibiotic usage, plays a crucial role in overall health. Therefore, this study aimed to investigate the prevalence of antibiotic resistant genes in the gut microbiota of Indonesian coastal and highland populations, as well as to identify vancomycin-resistant bacteria and their resistant genes.

Breastfeeding Rates During the COVID-19 Pandemic in Germany: Data from the CRONOS Registry.

SARS-CoV-2 infection and COVID-19 disease are thought to have an impact on breastfeeding rate - besides other known peripartal issues. Data of the national CRONOS registry regarding breastfeeding behavior in 6,746 women was analyzed regarding the time window between maternal SARS-CoV-2 infection and time of delivery. In addition, other influencing factors like the predominant viral variant, maternal disease severity, and gestational age at delivery were taken into account.

Calcineurin-independent NFATc1 signaling is essential for survival of Burkitt lymphoma cells.

In Burkitt lymphoma (BL), a tumor of germinal center B cells, the pro-apoptotic properties of MYC are controlled by tonic B cell receptor (BCR) signals. Since BL cells do not exhibit constitutive NF-B activity, we hypothesized that anti-apoptotic NFATc1 proteins provide a major transcriptional survival signal in BL. Here we show that post-transcriptional mechanisms are responsible for the calcineurin (CN) independent constitutive nuclear over-expression of NFATc1 in BL and - induced B cell lymphomas (BCL).

Excellent efficacy and beneficial safety during observational 5-year follow-up of rapid steroid withdrawal after renal transplantation (Harmony FU study).

Background: We previously reported excellent efficacy and improved safety aspects of rapid steroid withdrawal (RSWD) in the randomized controlled 1-year "Harmony" trial with 587 predominantly deceased-donor kidney transplant recipients randomized either to basiliximab or rabbit antithymocyte globulin induction therapy and compared with standard immunosuppressive therapy consisting of basiliximab, low tacrolimus once daily, mycophenolate mofetil and corticosteroids.

Methods: The 5-year post-trial follow-up (FU) data were obtained in an observational manner at a 3- and a 5-year visit only for those Harmony patients who consented to participate and covered clinical events that occurred from the second year onwards.

Results: Biopsy-proven acute rejection and death-censored graft loss rates remained low and independent of RSWD.

Pathogen-specific innate immune response patterns are distinctly affected by genetic diversity.

Innate immune responses vary by pathogen and host genetics. We analyze quantitative trait loci (eQTLs) and transcriptomes of monocytes from 215 individuals stimulated by fungal, Gram-negative or Gram-positive bacterial pathogens. We identify conserved monocyte responses to bacterial pathogens and a distinct antifungal response.

Intravenous injection of cyclosporin A loaded lipid nanocapsules fights inflammation and immune system activation in a mouse model of diabetic retinopathy.

Inflammation and immune system activation are key pathologic events in the onset and escalation of diabetic retinopathy (DR). Both are driven by cytokines and complement originating from the retinal pigment epithelium (RPE). Despite the RPE's pivotal role, there is no therapeutic tool to specifically interfere with the RPE-related pathomechanism.

Investigation of the Compatibility between Warheads and Peptidomimetic Sequences of Protease Inhibitors-A Comprehensive Reactivity and Selectivity Study.

Covalent peptidomimetic protease inhibitors have gained a lot of attention in drug development in recent years. They are designed to covalently bind the catalytically active amino acids through electrophilic groups called warheads. Covalent inhibition has an advantage in terms of pharmacodynamic properties but can also bear toxicity risks due to non-selective off-target protein binding.

HOW TO IDENTIFY SUBGROUPS IN LONGITUDINAL CLINICAL DATA: TREATMENT RESPONSE PATTERNS IN PATIENTS WITH A SHORTENED DENTAL ARCH.

Background: When dental patients seek care, treatments are not always successful,that is patients' oral health problems are not always eliminated or substantially reduced. Identifying these patients (treatment non-responders) is essential for clinical decision-making. Group-based trajectory modeling (GBTM) is rarely used in dentistry, but a promising statistical technique to identify non-responders in particular and clinical distinct patient groups in general in longitudinal data sets.

Photoactivated adenylyl cyclases attenuate sepsis-induced cardiomyopathy by suppressing macrophage-mediated inflammation.

Sepsis-induced myocardiopathy, characterized by innate immune cells infiltration and proinflammatory cytokines release, may lead to perfusion failure or even life-threatening cardiogenic shock. Macrophages-mediated inflammation has been shown to contribute to sepsis-induced myocardiopathy. In the current study, we introduced two photoactivated adenylyl cyclases (PACs), sp.

Is there a weekend effect in emergency surgery for colorectal carcinoma? Analysis from the German StuDoQ registry.

Background: Higher postoperative mortality has been observed among patients who received emergency colorectal surgery on the weekend compared to during the week. The aim of this study was to determine whether the weekday of emergency surgery affects the 30-day mortality and postoperative course in emergency colorectal surgery.

Methods: Prospectively acquired data from the 2010-2017 German StuDoQ|Colorectal surgery registries were analysed.

A single intravenous injection of cyclosporin A-loaded lipid nanocapsules prevents retinopathy of prematurity.

Retinopathy of prematurity (ROP) is a retinal disease that threatens the vision of prematurely born infants. Severe visual impairment up to complete blindness is caused by neovascularization and inflammation, progressively destroying the immature retina. ROP primarily affects newborns in middle- and low-income countries with limited access to current standard treatments such as intraocular drug injections and laser- or cryotherapy.

Don't look at me like that: Integration of gaze direction and facial expression.

Efficient decoding of facial expressions and gaze direction supports reactions to social environments. Although both cues are processed fast and accurately, when and how these cues are integrated is still debated. We investigated the temporal integration of gaze and emotion cues.

Diagnostic accuracy and feasibility of a rapid SARS-CoV-2 antigen test in general practice - a prospective multicenter validation and implementation study.

Background: PCR testing is considered the gold standard for SARS-CoV-2 diagnosis but its results are earliest available hours to days after testing. Rapid antigen tests represent a diagnostic tool enabling testing at the point of care. Rapid antigen tests have mostly been validated by the manufacturer or in controlled laboratory settings only.

Correlation Properties of Heart Rate Variability during a Marathon Race in Recreational Runners: Potential Biomarker of Complex Regulation during Endurance Exercise.

There is only very limited data examining cardiovascular responses in real-world endurance training/competition. The present study examines the influence of a marathon race on non-linear dynamics of heart rate (HR) variability (HRV). Eleven male recreational runners performed a self-paced marathon road race on an almost flat profile.

Molecular Profiling Reveals Characteristic and Decisive Signatures in Patients after Allogeneic Stem Cell Transplantation Suffering from Invasive Pulmonary Aspergillosis.

Despite available diagnostic tests and recent advances, diagnosis of pulmonary invasive aspergillosis (IPA) remains challenging. We performed a longitudinal case-control pilot study to identify host-specific, novel, and immune-relevant molecular candidates indicating IPA in patients post allogeneic stem cell transplantation (alloSCT). Supported by differential gene expression analysis of six relevant in vitro studies, we conducted RNA sequencing of three alloSCT patients categorized as probable IPA cases and their matched controls without infection (66 samples in total).

In Vitro and In Vivo Analysis of Ochratoxin A-Derived Glucuronides and Mercapturic Acids as Biomarkers of Exposure.

Ochratoxin A (OTA) is a widespread food contaminant, with exposure estimated to range from 0.64 to 17.79 ng/kg body weight (bw) for average consumers and from 2.

Real-Time Estimation of Aerobic Threshold and Exercise Intensity Distribution Using Fractal Correlation Properties of Heart Rate Variability: A Single-Case Field Application in a Former Olympic Triathlete.

A non-linear heart rate variability (HRV) index based on fractal correlation properties called alpha1 of Detrended Fluctuation Analysis (DFA-alpha1), has been shown to change with endurance exercise intensity. Its unique advantage is that it provides information about current absolute exercise intensity without prior lactate or gas exchange testing. Therefore, real-time assessment of this metric during field conditions using a wearable monitoring device could directly provide a valuable exercise intensity distribution without prior laboratory testing for different applied field settings in endurance sports.

Of Time Gals and Mega Men: Empirical Findings on Gender Differences in Digital Game Genre Preferences and the Accuracy of Respective Gender Stereotypes.

We investigated the accuracy of gender stereotypes regarding digital game genre preferences. In Study 1, 484 female and male participants rated their preference for 17 game genres (gender differences). In Study 2, another sample of 226 participants rated the extent to which the same genres were presumably preferred by women or men (gender stereotypes).

A revised instrument for the assessment of empathy and Theory of Mind in adolescents: Introducing the EmpaToM-Y.

Empathy and Theory of Mind (ToM) are two core components of social understanding. The EmpaToM is a validated social video task that allows for independent manipulation and assessment of the two capacities. First applications revealed that empathy and ToM are dissociable constructs on a neuronal as well as on a behavioral level.

Gastrointestinal epithelial innate immunity-regionalization and organoids as new model.

The human gastrointestinal tract is in constant contact with microbial stimuli. Its barriers have to ensure co-existence with the commensal bacteria, while enabling surveillance of intruding pathogens. At the centre of the interaction lies the epithelial layer, which marks the boundaries of the body.

A New Detection Method Defining the Aerobic Threshold for Endurance Exercise and Training Prescription Based on Fractal Correlation Properties of Heart Rate Variability.

The short-term scaling exponent alpha1 of detrended fluctuation analysis (DFA a1), a nonlinear index of heart rate variability (HRV) based on fractal correlation properties, has been shown to steadily change with increasing exercise intensity. To date, no study has specifically examined using the behavior of this index as a method for defining a low intensity exercise zone. The aim of this report is to compare both oxygen intake (VO) and heart rate (HR) reached at the first ventilatory threshold (VT1), a well-established delimiter of low intensity exercise, to those derived from a predefined DFA a1 transitional value.