Search Results (47)

Background/Objectives: Purinergic signaling, which involves extracellular ATP (eATP), its metabolites, purinergic receptors and ectonucleotidases, plays a pivotal role in the tumor microenvironment (TME), impacting tumor progression and the antineoplastic immune response. In this study, the CD39, CD73, P2X4, and P2X7 expression in NSCLC tumor cells and the surrounding stroma of 139 resected patients was examined. Methods: The study included tissue samples from 139 NSCLC patients. Tissue microarrays (TMAs) were constructed using 1.0 mm cores from annotated tumor regions. Immunohistochemical staining for CD39, CD73, P2X4, and P2X4 was performed on 2 µm sections. TMA slides were digitized and analyzed with QuPath, where staining intensity was evaluated using a semi-quantitative H-score. Statistical analysis, including survival analysis, was performed using R, to assess the impact of biomarker expression on patient outcomes. Results: High CD39 expression in both tumor and stromal cells was significantly associated with prolonged PFS (respectively: p = 0.0058 and p = 0.0067), particularly in adenocarcinoma (ADC) patients (respectively: p = 0.01 and p = 0.023). In the multivariable Cox model, low CD73 expression in tumor cells correlated with longer PFS (HR: 0.47; 95% CI: [0.28, 0.8], p = 0.005), while low CD73 expression in stromal cells was linked to increased progression risk (HR: 4.81; 95% CI: [1.61, 14.4], p = 0.001). Neither P2X7 nor P2X4 demonstrated a consistent effect on PFS in univariable analyses; however, multivariable analyses suggested that P2X4 might play a prognostic role in NSCLCs (HR: 0.37; 95% CI: [0.19, 0.73], p = 0.003). Conclusions: These findings underscore the importance of purinergic signaling in NSCLC prognosis and highlight the role of the ectonucleotidases CD39 and CD73 as potential therapeutic targets to enhance antineoplastic immune responses. Full article

The integration of distributed electric propulsion into a wing significantly alters the dynamic behavior of the wing. Consequently, the loads on the wing structure in service, in particular upon transient gust and landing impact loads, change substantially compared with conventional aircrafts with main engines mounted on the inner wing. As this might significantly increase the stress levels and number of load cycles, this paper assesses the impact of wing-integrated distributed propulsion on the fatigue behavior of the wing structure. This assessment is conducted based on a retrofit scenario of a conventional 19-seater commuter aircraft of the CS-23 category retrofitted with distributed electric propulsion. The wing structure is idealized with beam elements. Static and dynamic response analyses followed by stress analyses are conducted for typical load cases occurring during operation of the aircraft. The fatigue analysis is carried out based on the safe life approach. This study concludes that the integration of distributed electric propulsion has a substantial impact on the fatigue behavior of the wing. A significant increase in fatigue damage for the electric configurations compared with the conventional configuration is observed, in particular in the outer wing area. The increased damage accumulation is a result of the higher stress amplitudes and the longer decay duration of the structural vibrations due to gusts. The results suggest that adjustments to the structural design and maintenance procedures of future electric aircrafts may be necessary. Full article

The rapid expansion of lithium-ion batteries (LIBs), largely driven by the rising demand for electric vehicles, will lead to a significant increase in end-of-life (EOL) batteries, necessitating efficient recycling processes, which must be accompanied by equally efficient purification steps. This study addresses the challenge of reusing organic electrolyte solvents from spent LIBs, a key component often overlooked in existing recycling strategies. To address this issue, we developed a gas chromatography (GC) method. A variety of spent electrolyte samples of different origin, including mechanical-thermal pretreatment or direct cell recovery, were analyzed by quantification of common solvents and identified organic impurities. Results demonstrated that the composition of the recovered electrolytes was highly variable, with concentrations fluctuating. Impurities were identified, which may originate from various sources throughout the lifespan of an LIB and have the potential to reduce the performance of second-life LIBs by reusing the electrolyte without any purification. The findings highlight the necessity for advanced purification methods like a distillation process to remove these impurities and ensure the viability of recycled electrolytes in maintaining the performance and safety standards required for LIBs. This research contributes to the broader goal of enhancing the sustainability and reuse of battery materials. Full article

Here in this work, we report on micro-Raman spectroscopy investigations performed on freestanding Ni-rich NCM (Li_xNi_0.83Co_0.11Mn_0.06O₂) microcrystals transferred to flexible polyethylene terephthalate (PET) host substrates. This technological procedure introduces a first building block for future on-chip-integrated micro-accumulators for applications in flexible optoelectronics, sensors, microbiology, and human medicine. An after-synthesis thermal treatment was used to help improve the material homogeneity and perfection of the cathode material. To this end, a local laser micro-annealing process was applied to the freestanding Ni-rich NCM microcrystals. The thermally initialized structural processes in the singular micro-cathode units were characterized and determined by micro-Raman spectroscopy. Micro-Raman mapping images revealed the evolution of a recrystallization process after the local annealing procedure. Furthermore, laser micro-annealing led to the suppression of the pristine “polycrystalline morphology” of the investigated micro-cathode regions. Besides the dominant characteristic Raman mode at ~1085 cm⁻¹, most likely ascribed to lithium carbonate, metal oxides with Raman modes around ~550 cm⁻¹ were identified. This highly efficient transfer and integration technology represents a basic building block towards micrometer-sized accumulators for a large range of emerging applications. Full article

The aim of our cross-sectional and longitudinal study is to assess the relationship between daytime and night-time sleep duration and health-related quality of life (HRQoL) in adults with metabolic syndrome after a 1-year healthy lifestyle intervention. Analysis of the data from 2119 Spanish adults aged 55–75 years from the PREDIMED-Plus study was performed. Sleep duration was assessed using a wrist-worn accelerometer. HRQoL was measured using the SF-36 questionnaire. Linear regression models adjusted for socioeconomic and lifestyle factors and morbidity were developed. In cross-sectional analyses, participants with extreme night-time sleep duration categories showed lower physical component summary scores in Models 1 and 2 [β-coefficient (95% confidence interval) <6 h vs. 7–9 h: −2, 3 (−3.8 to −0.8); p = 0.002. >9 h vs. 7–9 h: −1.1 (−2.0 to −0.3); p = 0.01]. Participants who sleep less than 7 h a night and take a nap are associated with higher mental component summary scores [β-coefficient (95% confidence interval) 6.3 (1.3 to 11.3); p = 0.01]. No differences between night-time sleep categories and 12-month changes in HRQoL were observed. In conclusion, in cross-sectional analyses, extremes in nocturnal sleep duration are related to lower physical component summary scores and napping is associated with higher mental component summary scores in older adults who sleep less than 7 h a night. Full article

Anemia causes hypo-oxygenation in the brain, which could lead to cognitive disorders. We examined dietary iron intake as well as anemia markers (i.e., hemoglobin, hematocrit, mean corpuscular volume) and diabetes coexistence in relation to neuropsychological function and quality of life. In this study, 6117 community-dwelling adults aged 55–75 years (men) and 60–75 years (women) with overweight/obesity and metabolic syndrome were involved. We performed the Mini-Mental State Examination (MMSE), the Trail Making Test parts A and B (TMT-A/B), Semantic Verbal Fluency of animals (VFT-a), Phonological Verbal Fluency of letter P (VFT-p), Digit Span Test (DST), the Clock Drawing Test (CDT), and the Short Form-36 Health Survey (SF36-HRQL test). Dietary iron intake did not influence neuropsychological function or quality of life. However, anemia and lower levels of anemia markers were associated with worse scores in all neurophysiological and SF36-HRQL tests overall, but were especially clear in the MMSE, TMT-B (cognitive flexibility), and the physical component of the SF36-HRQL test. The relationships between anemia and diminished performance in the TMT-A/B and VFT tasks were notably pronounced and statistically significant solely among participants with diabetes. In brief, anemia and reduced levels of anemia markers were linked to inferior cognitive function, worse scores in different domains of executive function, as well as a poorer physical, but not mental, component of quality of life. It was also suggested that the coexistence of diabetes in anemic patients may exacerbate this negative impact on cognition. Nevertheless, dietary iron intake showed no correlation with any of the outcomes. To make conclusive recommendations for clinical practice, our findings need to be thoroughly tested through methodologically rigorous studies that minimize the risk of reverse causality. Full article

We demonstrate the successful implementation of an artificial neural network (ANN) to eliminate detrimental spectral shifts imposed in the measurement of laser absorption spectrometers (LASs). Since LASs rely on the analysis of the spectral characteristics of biological and chemical molecules, their accuracy and precision is especially prone to the presence of unwanted spectral shift in the measured molecular absorption spectrum over the reference spectrum. In this paper, an ANN was applied to a scanning grating-based mid-infrared trace gas sensing system, which suffers from temperature-induced spectral shifts. Using the HITRAN database, we generated synthetic gas absorbance spectra with random spectral shifts for training and validation. The ANN was trained with these synthetic spectra to identify the occurrence of spectral shifts. Our experimental verification unambiguously proves that such an ANN can be an excellent tool to accurately retrieve the gas concentration from imprecise or distorted spectra of gas absorption. Due to the global shift of the measured gas absorption spectrum, the accuracy of the retrieved gas concentration using a typical least-mean-squares fitting algorithm was considerably degraded by 40.3%. However, when the gas concentration of the same measurement dataset was predicted by the proposed multilayer perceptron network, the sensing accuracy significantly improved by reducing the error to less than ±1% while preserving the sensing sensitivity. Full article

According to Cloninger’s model, personality is conceptualized in temperament and character traits contributing to a child’s psychosocial development. Additionally, parent–child interaction is important for the child’s socio-emotional development. To date, the relationship between attachment and temperament and character for child mental health development and its effects on parents remains mostly unclear. The aim of the present study was thus to examine the relationship of attachment, temperament and character, parental stress, and mental health problems among 125 children (mean age = 7.14 years) in Switzerland. Temperament and character, attachment disorder (symptoms), parental stress, and mental health problems were assessed with psychometric questionnaires; attachment was assessed with an additional observational measure. Descriptive characters of the sample were presented, and group differences and correlations were computed. For temperament traits, results revealed significant group differences for novelty seeking and persistence and attachment disorder types. For character traits, the findings showed significant group differences for self-directedness and cooperativeness and attachment disorder types. Moderate effect sizes for groups differences were found. Further, the mixed-type (inhibited and disinhibited) and inhibited attachment disorder type were the most burdened groups. The present findings suggest that temperament and character traits, as well as parental stress and mental health problems are associated with the occurrence of attachment disorders among children. Future longitudinal studies with larger samples are needed to examine the causal relationships of temperament and character with attachment, including person-related and environmental factors among children. Full article

Background: Cardiac autonomic dysfunction (CADF) is a major contributor to increased cardiac mortality in schizophrenia patients. The aberrant function of voltage-gated ion channels, which are widely distributed in the brain and heart, may link schizophrenia and CADF. In search of channel-encoding genes that are associated with both CADF and schizophrenia, CACNA1C and KCNH2 are promising candidates. In this study, we tested for associations between genetic findings in both genes and CADF parameters in schizophrenia patients whose heart functions were not influenced by psychopharmaceuticals. Methods: First, we searched the literature for single-nucleotide polymorphisms (SNPs) in CACNA1C and KCNH2 that showed genome-wide significant association with schizophrenia. Subsequently, we looked for such robust associations with CADF traits at these loci. A total of 5 CACNA1C SNPs and 9 KCNH2 SNPs were found and genotyped in 77 unmedicated schizophrenia patients and 144 healthy controls. Genotype-related impacts on heart rate (HR) dynamics and QT variability indices (QTvi) were analyzed separately in patients and healthy controls. Results: We observed significantly increased QTvi in unmedicated patients with CADF-associated risk in CACNA1C rs2283274 C and schizophrenia-associated risk in rs2239061 G compared to the non-risk allele in these patients. Moreover, unmedicated patients with previously identified schizophrenia risk alleles in KCNH2 rs11763131 A, rs3807373 A, rs3800779 C, rs748693 G, and 1036145 T showed increased mean HR and QTvi as compared to non-risk alleles. Conclusions: We propose a potential pleiotropic role for common variation in CACNA1C and KCNH2 associated with CADF in schizophrenia patients, independent of antipsychotic medication, that predisposes them to cardiac arrhythmias and premature death. Full article

Post-COVID-19 syndrome (PCS) is characterized by persisting sequelae after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). PCS can affect patients with all COVID-19 disease severities. As previous studies have revealed impaired blood flow as a provoking factor triggering PCS, it was the aim of the present study to investigate the potential association between self-reported chronic fatigue and retinal microcirculation in patients with PCS, potentially indicating an objective biomarker. A prospective study was performed, including 201 subjects: 173 patients with PCS and 28 controls. Retinal microcirculation was visualized by OCT angiography (OCT-A) and quantified using the Erlangen-Angio-Tool as macula and peripapillary vessel density (VD). Chronic fatigue (CF) was assessed according to the variables of Bell’s score, age and gender. VDs in the superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) were analyzed, considering the repetitions (12 times). Seropositivity for autoantibodies targeting G protein-coupled receptors (GPCR-AAbs) was determined by an established cardiomyocyte bioassay. Taking account of the repetitions, a mixed model was performed to detect possible differences in the least square means between the different groups included in the analysis. An age effect in relation to VD was observed between patients and controls (p < 0.0001). Gender analysis showed that women with PCS showed lower VD levels in the SVP compared to male patients (p = 0.0015). The PCS patients showed significantly lower VDs in the ICP as compared to the controls (p = 0.0001 (CI: 0.32; 1)). Moreover, considering PCS patients, the mixed model revealed a significant difference between those with chronic fatigue (CF) and those without CF with respect to VDs in the SVP (p = 0.0033 (CI: −4.5; −0.92)). The model included variables of age, gender and Bell’s score, representing a subjective marker for CF. Consequently, retinal microcirculation might serve as an objective biomarker in subjectively reported chronic fatigue in patients with PCS. Full article

We report on a novel, cost-effective non-dispersive infrared (NDIR) multi-gas sensor aimed at environmental air pollution monitoring. The rugged design of the K96 sensor core combines highest compactness and low-power consumption with our unique multi-channel cell design, featuring the detection of up to three different gases simultaneously, including CO₂, CH₄, N₂O, and H₂O. Our sensing platform allows the selection of the target gases as well as the concentration ranges, thus providing highly customizable gas sensor systems targeting application-specific gas monitoring settings. The sensor core comes with an implemented calibration model, and can address in real time any cross-sensitivity between the NDIR gas-sensing channels. We provide an immensely versatile sensing system while ensuring high sensing stability combined with high precision (<0.1 ppm for both CO₂ and N₂O, <0.5 ppm for CH₄). The K96 multi-gas sensor core offers a resilient sensor solution for the increasing demand of compact monitoring systems in the field of environmental monitoring at reasonable costs for medium-to-high volumes. Full article

Apart from Alzheimer’s disease (AD), no biomarkers for the differential diagnosis of dementia have been established to date. Inflammatory processes contribute to the pathogenesis of dementia subtypes, e.g., AD or frontotemporal dementia (FTD). In the context of cancer or cardiovascular diseases, white blood cell (WBC) populations and platelet counts, as well as C-reactive protein (CRP), have emerged as biomarkers. Their clinical relevance in dementia, however, is currently only insufficiently investigated. In the present study, hematological and inflammatory parameters were measured in the peripheral blood of 97 patients admitted to the gerontopsychiatric ward of Hannover Medical School, a university hospital in Germany, for dementia assessment. The study population comprised 20 non-demented, depressed patients (control group) and 77 demented patients who were assigned to five different groups based on their underlying dementia etiology: AD, n = 33; vascular dementia, n = 12; mixed dementia, n = 21; FTD, n = 5; and Korsakoff syndrome, n = 6. We observed neither statistically significant differences regarding total WBC populations, platelet counts, neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio, nor CRP levels between the control group and the five dementia groups. CRP levels tended to be higher in patients with Korsakoff syndrome than in the control group and in AD patients. Thus, CRP could possibly play a role in the differential diagnosis of dementia. This should be investigated further in future prospective studies with larger sample sizes. WBC and platelet counts, by contrast, do not appear to be suitable biomarkers in the differential diagnosis of dementia. Full article

SARS-CoV-2 was first detected in 2019 in Wuhan, China. It has been found to be the most pathogenic virus among coronaviruses and is associated with endothelial damage resulting in respiratory failure. Determine whether heparanase and heparan sulfate fragments, biomarkers of endothelial function, can assist in the risk stratification and clinical management of critically ill COVID-19 patients admitted to the intensive care unit. We investigated 53 critically ill patients with severe COVID-19 admitted between March and April 2020 to the University Hospital RWTH Aachen. Heparanase activity and serum levels of both heparanase and heparan sulfate were measured on day one (day of diagnosis) and day three in patients with COVID-19. The patients were classified into four groups according to the severity of ARDS. When compared to baseline data (day one), heparanase activity increased and the heparan sulfate serum levels decreased with increasing severity of ARDS. The heparanase activity significantly correlated with the lactate concentration on day one (r = 0.34, p = 0.024) and on day three (r = 0.43, p = 0.006). Heparanase activity and heparan sulfate levels correlate with COVID-19 disease severity and outcome. Both biomarkers might be helpful in predicting clinical course and outcomes in COVID-19 patients. Full article

Primary hepatocytes are a major tool in biomedical research. However, obtaining high yields of variable hepatocytes is technically challenging. Most protocols rely on the two-step collagenase perfusion protocol introduced by Per Ottar Seglen in 1976. In this procedure, the liver is perfused in situ with a recirculating, constant volume of calcium-free buffer, which is maintained at 37 °C and continuously oxygenated. In a second step, the liver is removed from the carcass and perfused with a collagenase solution in order to dissociate the extracellular matrix of the liver and liberate individual cells. Finally, the dissected hepatocytes are further purified and concentrated by density-based centrifugation. However, failure in proper cannulation, incomplete enzymatic digestion or over-digestion can result in low cell yield and viability. Here we present a novel semi-automated perfusion device, which allows gentle, rapid and efficient generation of a single-cell suspension from rodent livers. In combination with prefabricated buffers, the system allows reliable and highly reproducible isolation of primary hepatocytes. Full article

Background: In reconstructive surgery, loss of a microvascular free flap due to perfusion disorders, especially thrombosis, is a serious complication. In recent years, viscoelastic testing (VET) has become increasingly important in point-of-care (POC) anticoagulation monitoring. This paper describes a protocol for enhanced anticoagulation monitoring during maxillofacial flap surgery. Objective: The aim of the study will be to evaluate, in a controlled setting, the predictive value of POC devices for the type of flap perfusion disorders due to thrombosis or bleeding. VET, Platelet monitoring (PM) and standard laboratory tests (SLT) are comparatively examined. Methods/Design: This study is an investigator-initiated prospective trial in 100 patients undergoing maxillofacial surgery. Patients who undergo reconstructive surgery using microvascular-free flaps will be consecutively enrolled in the study. All patients provide blood samples for VET, PM and SLT at defined time points. The primary outcome is defined as free flap loss during the hospital stay. Statistical analyses will be performed using t-tests, including the Bonferroni adjustment for multiple comparisons. Discussion: This study will help clarify whether VET can improve individualized patient care in reconstruction surgery. A better understanding of coagulation in relation to flap perfusion disorders may allow real-time adaption of antithrombotic strategies and potentially prevent flap complications. Full article