Search Results (948)

Focal chondral defects of the knee are a common cause of pain and functional limitation in active individuals and may predispose to early degenerative joint changes. Given the limited regenerative capacity of hyaline cartilage, biologically based surgical strategies have emerged to promote tissue repair and restore joint function. This narrative review critically examines current treatment approaches that rely on autologous cell sources and scaffold-supported regeneration. Particular emphasis is placed on techniques that stimulate endogenous repair or support chondrocyte-based tissue restoration through the use of autologous biomaterial constructs. The influence of lesion morphology, joint biomechanics, and patient-specific variables on treatment selection is discussed in detail, focusing on the differences between tibiofemoral and patellofemoral involvement. Biologically driven approaches have shown promising mid- to long-term outcomes in selected patients, and are increasingly favoured over traditional methods in specific clinical scenarios. However, the literature remains limited by heterogeneity in study design, follow-up duration, and outcome measures. This review aims to provide an evidence-based, morphology-informed framework to support the clinical decision-making process in the management of knee cartilage defects. Full article

Background: Consolidation therapy with durvalumab after definitive chemoradiotherapy (CRT) has become the standard care for patients with stage III non-small-cell lung cancer (NSCLC) following the PACIFIC trial. However, real-world data evaluating outcomes under routine clinical conditions remain limited, particularly in European cohorts. Methods: In this retrospective single-center study, we analyzed clinical data from 72 patients with stage III NSCLC treated with definitive CRT between 2017 and 2022. The patients were stratified by receipt of durvalumab consolidation. Univariable and multivariable Cox regression models were used to assess overall survival (OS) and progression-free survival (PFS). Stepwise variable selection based on the Akaike Information Criterion (AIC) was used to construct an optimized multivariable model. A sensitivity analysis with adjustment for treatment period (2017–2018 vs. 2019–2022) was conducted to account for the introduction of durvalumab into routine clinical practice. Results: Among 72 patients, 35 received durvalumab and 37 did not. The median OS was 2.08 years; the 3- and 5-year OS rates were 38.6% and 30.3%, respectively. Multivariable regression revealed significantly improved OS associated with Karnofsky performance status (KPS) > 80% (HR 0.29, p = 0.003), Charlson Comorbidity Index (CCI) ≤ 2 (HR 0.39, p = 0.009), and durvalumab treatment (HR 3.99, p = 0.008). PD-L1 expression ≥ 1% showed a trend toward improved OS (HR 3.72, p = 0.063). The median progression-free survival (PFS) for the total cohort was 1.17 years. The estimated 3- and 5-year PFS rates were 31.1% and 26.3%, respectively. Patients treated with durvalumab had a longer median PFS (20.5 months) compared to those without durvalumab (12.0 months). In the multivariable analysis, KPS > 80% (HR 0.29, p < 0.001), CCI ≤ 2 (HR 0.53, p = 0.048), and durvalumab treatment (HR 2.81, p = 0.023) were significantly associated with improved PFS. A sensitivity analysis adjusting for treatment period—reflecting the introduction of durvalumab into routine clinical practice from 2019—confirmed the robustness of these findings. Conclusions: Our findings support the clinical benefit of durvalumab consolidation following CRT in a real-world population, especially in patients with good performance status and low comorbidity burden. These results confirm and extend the PACIFIC trial findings into routine clinical practice, highlighting the prognostic value of functional status and comorbidity alongside PD-L1 expression. Full article

Background: Adolescents’ subjective well-being (SWB) is a key indicator of quality of life. While its development during schooling has been widely studied, few studies have examined changes in SWB after leaving school due to the need for longitudinal data. This study investigates changes in SWB among adolescents in Germany over the two years before and after leaving school, focusing on school type, socioeconomic position, gender, and family structure. Methods: We use data from the ninth-grade cohort of the German National Educational Panel Study, first surveyed in 2010 and followed annually. Growth modeling (specifically, a multilevel discontinuity model) is applied to analyze SWB trajectories and potential moderation by background characteristics. The final sample includes 19,767 observations from 6599 individuals. Results: SWB increases notably after leaving school and remains stable before and after the transition. The increase is smaller for adolescents completing higher secondary education, living in nuclear families, or identifying as male. These groups report higher SWB prior to the transition, so post-school changes reduce group differences. Conclusion: The findings suggest that schools may lack adequate resources to support adolescents in mastering key developmental challenges. While school is a critical environment, it may also impose pressures that are associated with lower well-being. Full article

Objectives: The aim of this study was to assess the association of diabetes mellitus and its medications with overall response (ORR) and mortality or cancer-specific survival (CSS) in patients with metastatic urothelial cancer receiving enfortumab vedotin monotherapy. Methods: This multicentre retrospective cohort study was designed according to the guidelines for the synthesis of qualitative research (ENTREQ). Eligible patients were adults (≥18) years treated with enfortumab vedotin monotherapy for metastatic urothelial cancer between June 2024 and January 2025. A total of 125 patients were reported across 11 centres. Results: The cohort included 93 males (74.4%) and 32 females (25.6%), with a mean age of 68.3 years (SD 9.3). The primary tumour site was the bladder in 109 (87.2%) cases and the upper tract (UTUC) in 16 (12.8%) cases. Interestingly, medication with metformin was significantly associated with cancer-specific mortality (37.9% versus 77.8%; p = 0.019), while patients with insulin-dependent diabetes mellitus had a significantly better CSS (Log Rank = 0.004). Upon comparing only patients who already had diabetes mellitus and then received anti-diabetic medication, there was a significant association between patients with diabetes mellitus receiving metformin and a worse 3-month ORR (80.0% versus 55.6%; p = 0.039). Regarding the subpopulation of UTUC, cancer-specific mortality was significantly associated with metformin medication (p = 0.033). Conclusions: Despite recent reports that metformin has protective effects in urothelial cancer, our findings suggest that metformin use may be linked to worse responses and survival outcomes in patients treated with enfortumab vedotin monotherapy. Further research, particularly translational research into the underlying diabetic and pharmacologic pathways, is warranted. Full article

It was unknown whether hyperthermia increased the efficacy of histamine to raise the force of cardiac contractions via human H1-histamine receptors. To that end, we measured the force in isolated human atrial preparations (HAPs) excised from the right atrium of patients who underwent cardiac surgery due to severe two- or three-vessel coronary heart disease. For comparison, we also measured the force in paced (1 Hz) left and spontaneously beating right atrial preparations of transgenic mice overexpressing cardiac human H1-histamine receptors (H1-TG). Histamine (100 µM) was less efficient in raising the force in left atrial preparations from H1 TG mouse atria under hyperthermia than under hypothermia. Oppositely, histamine was more efficient in augmenting force during hyperthermia than during hypothermia in isolated electrically stimulated (1 Hz) HAPs. In sum, the contractile response to activation of H1-histamine receptor in H1-TG mice and in HAPs are opposite with regard to hyperthermia dependence. In patients with fever, histamine might thus be important, to preserve cardiac contractile function as a compensatory mechanism. Full article

The increasing popularity of “superseeds” such as flax, sesame, amaranth and quinoa as functional foods raises the need for robust analytical methods for authentication purposes. In this work, a standardized workflow for the extraction, characterization and identification of unique peptides that may be used as markers to distinguish superseed species was investigated. Ammonium bicarbonate/urea (Ambi/urea) extraction, sodium dodecyl sulfate (SDS) buffer and trichloroacetic acid (TCA) precipitation were initially implemented and, based on the level and composition of the extracted proteins, the SDS buffer protocol was selected. Electrophoresis analysis revealed consistent protein profiles between biological replicates from each of the eleven seed species, confirming the reproducibility of the SDS buffer protocol. Targeted mass spectrometry successfully identified species-specific peptide markers for six of eleven superseeds investigated, including peptides from conlinins in flaxseed (WVQQAK), 11S globulins in sesame (LVYIER), oleosin in quinoa (DVGQTIESK), agglutin-like lectins in amaranth (CAGVSVIR), as well as cupin-like proteins in poppy seeds (INIVNSQK) and edestins in hemp seeds (FLQLSAER). Moreover, proteome cross-analysis allowed us to disqualify the isomeric peptide LTALEPTNR from 11S globulins present in amaranth and quinoa. However, no reliable markers were identified for chia, canihua, basil, black cumin, and psyllium seeds under current conditions. While this targeted proteomics approach shows promise for superseed authentication, comprehensive method validation and alternative strategies for marker-deficient species are required before routine implementation. Full article

Farmers face increasing pressure to maintain vital populations of the critically endangered field hamster (Cricetus cricetus) while managing crop damage caused by field mice. This challenge is linked to the UN Sustainable Development Goals (SDGs) 2 and 15, addressing food security and biodiversity. Consequently, the reliable detection of hamster activity in agricultural fields is essential. While remote sensing offers potential for wildlife monitoring, commonly used RGB imagery has limitations in detecting small burrow entrances in vegetated areas. This study investigates the potential of drone-based Light Detection and Ranging (LiDAR) data for identifying field hamster burrow entrances in agricultural landscapes. A geostatistical method was developed to detect local elevation minima as indicators of burrow openings. The analysis used four datasets captured at varying flight altitudes and spatial resolutions. The method successfully detected up to 20 out of 23 known burrow entrances and achieved an F1-score of 0.83 for the best-performing dataset. Detection was most accurate at flight altitudes of 30 m or lower, with performance decreasing at higher altitudes due to reduced point density. These findings demonstrate the potential of UAV-based LiDAR to support non-invasive species monitoring and habitat management in agricultural systems, contributing to sustainable conservation practices in line with the SDGs. Full article

In water-scarce regions, natural ecosystems and agriculture increasingly compete for limited water resources, intensifying stress during periods of drought. To assess these competing demands, we applied a modified PT-JPL model that incorporates the thermal inertial approach as a substitute for relative humidity (RH) in estimating soil evaporation—a method that significantly outperforms the original PT-JPL formulation in Mediterranean semi-arid irrigated areas. This remote sensing framework enabled us to quantify spatial and temporal variations in water use across both natural and agricultural systems within the UNESCO World Heritage site of Doñana. Our analysis revealed an increasing evapotranspiration (ET) trend in intensified agricultural areas and rice fields surrounding the National Park (R = 0.3), contrasted by a strong negative ET trend in wetlands (R < −0.5). These opposing patterns suggest a growing diversion of water toward irrigation at the expense of natural ecosystems. The impact was especially marked during droughts, such as the 2011–2016 period, when precipitation declined by 16%. In wetlands, ET was significantly correlated with precipitation (R > 0.4), highlighting their vulnerability to reduced water inputs. These findings offer crucial insights to support sustainable water management strategies that balance agricultural productivity with the preservation of ecologically valuable systems under mounting climatic and anthropogenic pressures typical of semi-arid Mediterranean environments. Full article

Stones in agricultural fields pose a recurring challenge, particularly due to their potential to damage agricultural machinery and disrupt field operations. As modern agriculture moves toward automation and precision farming, efficient stone detection has become a critical concern. This study explores the potential of thermal imaging as a non-invasive method for detecting stones under varying environmental conditions. A series of controlled laboratory experiments and field investigations confirmed the assumption that stones exhibit higher surface temperatures than the surrounding soil, especially when soil moisture is high and air temperatures are cooling rapidly. This temperature difference is attributed to the higher thermal inertia of stones, which allows them to absorb and retain heat longer than soil, as well as to the evaporative cooling from moist soil. These findings demonstrate the viability of thermal cameras as a tool for stone detection in precision farming. Incorporating this technology with GPS mapping enables the generation of accurate location data, facilitating targeted stone removal and reducing equipment damage. This approach aligns with the goals of sustainable agricultural engineering by supporting field automation, minimizing mechanical inefficiencies, and promoting data-driven decisions. Thermal imaging thereby contributes to the evolution of next-generation agricultural systems. Full article

Poly(ADP-ribose) polymerases (PARP) are a family of enzymes that were proven to play an essential role in the initiation and activation of DNA repair processes in the case of DNA single-strand breaks. The inhibition of PARP enzymes might be a promising option for the treatment of several challenging types of cancers, including triple-negative breast cancer (TNBC) and non-small cell lung carcinoma (NSCLC). This study utilizes several techniques to screen the compound collection of the Leibniz Institute of Plant Biochemistry (IPB) to identify novel hPARP-1 inhibitors. First, an in silico pharmacophore-based docking study was conducted to virtually screen compounds with potential inhibitory effects. To evaluate these compounds in vitro, a cell-free enzyme assay was developed, optimized, and employed to identify hPARP-1 inhibitors, resulting in the discovery of two novel scaffolds represented by compounds 54 and 57, with the latter being the most active one from the compound library. Furthermore, fluorescence microscopy and synergism assays were performed to investigate the cellular and nuclear pathways of hPARP-1 inhibitor 57 and its potential synergistic effect with the DNA-damaging agent temozolomide. The findings suggest that the compound requires further lead optimization to enhance its ability to target the nuclear PARP enzyme effectively. Nonetheless, this new scaffold demonstrated a five-fold higher PARP inhibitory activity at the enzyme level compared to the core structure of olaparib (OLP), phthalazin-1(2H)-one. Full article

We report on the preparation and characterization of a new family of hydrogen-bonded nematogenic liquid crystalline dimers. The dimers are supramolecular complexes that consist of a benzoic acid derivative, acting as the proton donor, featuring a spacer with seven methylene groups and a terminal decyloxy chain, paired with an azopyridine derivative as the proton acceptor. The latter was either fluorinated or nonfluorinated with variable alkoxy chain length. The formation of a hydrogen bond between the individual components was confirmed using FTIR and ¹H NMR spectroscopy. All supramolecules were investigated for their liquid crystalline behaviour via a polarized optical microscope (POM) and differential scanning calorimetry (DSC). All materials exhibit enantiotropic nematic phases as confirmed by X-ray diffraction (XRD) and POM investigations. The nematic phase range depends strongly on the degree and position of fluorine atoms. Additionally, the supramolecules demonstrated a rapid and reversible transition between the liquid crystal phase and the isotropic liquid state because of trans-cis photoisomerization upon light irradiation. Therefore, this study presents a straightforward approach to design photo-responsive nematic materials, which could be of interest for nonlinear optics applications. Full article

This study aimed to systematically review the literature of the last 24 years to determine the influence of dam heat stress, nutrition, body condition, vaccination, parity, and twin pregnancy on calf morbidity and mortality. The systematic search was carried out using PubMed, CAB Abstracts, and Web of Science databases. The final number of included studies was 11 for heat stress, 21 for nutrition, 11 for body condition, 11 for vaccination, 23 for parity, and 18 for twin pregnancy. The body condition score, parity, and twin pregnancy had an influence on perinatal mortality. Vaccination, parity, and twin pregnancy had an influence on mortality up to weaning. Heat stress, nutrition, and twin pregnancy had an influence on the immunoglobulin transfer to the calves. Nutrition, body condition score, vaccination, and parity had an influence on morbidity. This systematic review provides evidence that prenatal factors have an influence on calf morbidity and mortality. Full article

Background/Objectives: Comparative analysis of work ability factors between German nurses without a migration background and Kosovar nurses working in Germany as nurses with a migration background. Methods: This is an observational cross-sectional study. We surveyed 814 nurses from hospitals in Kosovo and Germany using self-administered questionnaires. We used the Nurses Working Capability (WiN) Screening Manual to analyze work ability factors. Data analysis involved descriptive statistics, ANCOVA, and Bonferroni multiple comparison tests. Results: Of the 40 target factors, 17 showed significant differences. There were notable distinctions between German and Kosovar nurses in Germany. Concerning health and personal resources, Kosovar nurses in Germany reported poorer physical (M = 3.71) and social health (M = 3.83) but better mental health (M = 3.53) and fewer cognitive stress symptoms (M = 3.60) than German nurses (M = 3.97, M = 4.05, M = 3.40, and M = 4.00, respectively). As to the work-related factors, Kosovar nurses in Germany faced higher emotional demands (M = 3.33), felt greater time pressure (M = 3.43), and had a more negative view of the organizational structure (M = 2.09) but rated supervisor feedback more positively (M = 3.24) and faced fewer patient-related stressors (M = 2.16) relative to German nurses (M = 2.64, M = 2.64, M = 2.82, M = 2.76, and M = 3.09, respectively). Conclusions: Kosovar immigrant nurses in Germany face distinct challenges related to physical and social health, higher emotional demands, and time constraints; they also have a more negative view of organizational structure than native German nurses. The possible causes of these differences may be attributed to migration-related stress, cultural and environmental adaptations, varying job expectations, or organizational experiences. Full article

Background/Objectives: CD47 is a cell surface glycoprotein moderately expressed in healthy cells and upregulated in cancer and viral infected cells. CD47’s interaction with signal regulatory protein alpha (SIRPα) inhibits phagocytic cells and its interaction with thrombospondin-1 inhibits T cell response. Experimental evidence has revealed that the blockade of CD47 resulted in the increased activation and function of both innate and adaptive immune cells, therefore exerting antitumoral and antiviral effects. Recent studies have shown that the combination of vaccines and immune checkpoint inhibitors could be a promising approach to increasing vaccine immunogenicity. Here, we investigated the vaccinal effect of anti-CD47 antibodies and discussed the possibilities of combining anti-CD47 treatments with vaccines. Methods: Using vesicular stomatitis virus (VSV), a widely used replication-competent vaccine vector, we evaluated the impact of the immunotherapeutic blockade of CD47 on cellular, humoral, and protective immunity. We infected C57BL/6 mice with VSV, treated them with anti-CD47 antibodies or an isotype, and evaluated the total immunoglobulin (Ig), IgG neutralizing antibodies, B cell activation, CD8+ T cell effector function, and survival of the mice. Results: We found that the treatments of anti-CD47 antibodies led to significantly increased Ig and IgG neutralizing antibody levels compared to the isotype treatment. Flow cytometric analysis of B cells revealed no difference in the number of circulating B cells; however, we observed an increased surface expression of CD80 and CD86 in B cells among anti-CD47-treated mice. Further analysis of the impact of CD47 blockade on T immunity revealed a significantly higher percentage of IFN-γ⁺ CD4 and IFN-γ⁺ CD8 T cells in anti-CD47-treated mice. Upon infecting mice with a lethal VSV dose, we observed a significantly higher survival rate among the anti-CD47-treated mice compared to control mice. Conclusions: Our results indicate that anti-CD47 treatment induces a stronger cellular and humoral immune response, leading to better protection. As such, immunotherapy by CD47 blockade in combination with vaccines could be a promising approach to improve vaccine efficacy. Full article

This study focuses on the extraction, characterization, and biological evaluation of diterpenes from green coffee beans, specifically, cafestol and kahweol. These compounds, known for their potential health benefits, were isolated via optimized extraction and saponification processes. Separation was achieved using silver nitrate-impregnated silica gel, and structural elucidation was performed through advanced 1D and 2D NMR techniques, including HSQC, HMBC, and (IN)ADEQUATE. Due to kahweol’s instability, the research prioritized cafestol for the synthesis of rhodamine B conjugates. Initial ester-linked conjugates proved unstable, prompting the development of more robust derivatives through amide linkage strategies and further functionalization via acetylation and oxidation reactions. Some oxidation methods led to furan ring cleavage, impacting structural integrity. Selected compounds were tested for cytotoxicity using SRB assays on human tumor cell lines (MCF7, A2780) and non-malignant fibroblasts (NIH 3T3). While the parent diterpenes and many derivatives showed minimal activity, several cafestol–rhodamine B conjugates demonstrated notable cytotoxic effects. Compound 6, in particular, exhibited selective activity against cancer cells with reduced toxicity toward non-malignant cells. Full article