Search Results (55)

Background: Soft-tissue sarcomas (STSs) represent a heterogeneous group of malignancies with widely varying treatment responses and biological behaviors. While spontaneous necrosis (present at diagnosis) is recognized in established sarcoma grading systems, the prognostic significance of therapy-induced necrosis remains uncertain. Inconsistent definitions, methodological variability, and clinical confounders further complicate the interpretation of necrosis as an independent prognostic marker. Methods: This communication synthesizes findings from an international, multidisciplinary webinar hosted by the Sarcoma Academy, critically assessing the utility of therapy-induced necrosis in STS management. Discussions encompassed surgical, pathological, oncological, and radiological perspectives, emphasizing how necrosis is defined, measured, and contextualized in patient care. Results: Heterogeneity in STS subtypes, varied treatment protocols, and sampling inconsistencies challenge the prognostic value of post-treatment necrosis. While substantial necrosis may sometimes signal effective therapy, it can also reflect the tumor’s aggressive nature. The panel underscored the utility of measuring the percentage of viable tumor cells, rather than necrosis alone, to obtain a more standardized and reproducible measure of therapy response. Emerging approaches—such as radiomics, molecular profiling, immune-based analyses, and real-world evidence (RWE) protocols—offer promising avenues for refining prognostication and guiding personalized therapy in STS. Conclusions: A focus solely on therapy-induced necrosis is insufficient to predict outcomes in STS. Instead, a multidisciplinary framework—combining standardized pathology protocols, quantification of viable tumor cells, advanced imaging, and innovative clinical trial designs—can better capture both treatment effects and underlying tumor biology. Future collaborative studies and hybrid trial methodologies are needed to determine which STS subgroups gain the most from intensified treatments aimed at maximizing necrosis, and how to balance such interventions with surgical considerations, toxicity, and overall patient well-being. Full article

Background: There are no clinical or laboratory markers that can diagnose acute mesenteric ischemia (AMI) accurately. This study aimed to find differences in clinical and laboratory markers between arterial occlusive AMI and other acute abdominal diseases where AMI was initially suspected. Methods: This was a post hoc study of an international prospective multicenter study where data on patients with suspected AMI were collected. Independent factors associated with arterial occlusive AMI were evaluated in a multivariable logistic regression analysis. Results: The number of patients with arterial occlusive AMI was 231, consisting of thrombotic (n = 104), embolic (n = 61), and indeterminate (n = 66) occlusions. The non-AMI group included 287 patients, of whom 128 had strangulated bowel obstruction. Current smoking (odds ratio [OR] 2.56, 95% confidence interval [CI] 1.31–5.03), hypertension (OR 2.08, 95% CI 1.09–3.97), bowel emptying (OR 3.25, 95% CI 1.59–6.63), and leukocytosis (OR 1.54, 95% CI 1.14–2.08) at admission were independently associated with arterial occlusive AMI compared to the non-AMI group. Conclusions: This study found clinical and laboratory data to be associated with arterial occlusive AMI in patients with suspicion of AMI, which can possibly be of value in screening for arterial occlusive AMI at the emergency department. Further studies are needed to find more accurate diagnostic markers. Full article

(1) Background: Compared to medical personnel, SARS-CoV-2mRNA vaccination-related positive immunity rates, levels, and preservation over time in dialysis and kidney transplant patients are reduced. We hypothesized that COVID-19 pre-exposure influences both vaccination-dependent immunity development and preservation in a group-dependent manner. (2) Methods: We evaluated 2- and 9-month follow-up data in our observational Dia-Vacc study, exploring specific cellular (interferon-γ release assay = IGRA) and/or humoral immune responses (IgA/IgG/RBD antibodies) after two SARS-CoV-2mRNA vaccinations in 2630 participants, including medical personnel (301-MP), dialysis patients (1841-DP), and kidney transplant recipients (488-KTR). Study participants were also separated into COVID-19 pre-exposure (hybrid immunity) positive (n = 407) versus negative (n = 2223) groups. (3) Results: COVID-19 pre-exposure improved most vaccination-related positive immunity rates in KTR and DP at 2 months but not in MP, where rates reached almost 100% independent of hybrid immunity. In the COVID-19-negative study, patients’ immunity faded between two and nine months, evaluated via the percentage of patients with an RBD antibody decrease >50%, and was markedly group- (MP-17.8%, DP-52.2%, and KTR-38.6%) and vaccine type-dependent. In contrast, in all patient groups with COVID-19, pre-exposure RBD antibody decreases of >50% were similarly rare (MP-4.3%, DP-7.2%, and KTR-0%) but still vaccine type-dependent, with numerically reduced numbers in mRNA-1273- versus BNT162b2mRNA-treated patients. Multivariable regression analysis of RBD antibody changes between two and nine months by interval scale categorization confirmed COVID-19 pre-exposure as a factor in inhibiting strong RBD Ab fading. COVID-19 pre-exposure in MP and DP also numerically reduced T-cell immunity fading. In DP, symptomatic (versus asymptomatic) COVID-19 pre-exposure was identified as a factor in reducing strong RBD Ab fading after vaccination. (4) Conclusions: After mRNA vaccination, immunity positivity rates in DP and KTR but not MP, as well as immunity preservation in MP/DP/KTR, are markedly improved via prior COVID-19 infection. In DP, prior symptomatic compared to asymptomatic COVID-19 disease was particularly effective in blocking immunity fading after mRNA vaccination. Full article

As chronic illness is common among older people, self-care practices for older people are needed to control health status, to prevent possible complications and to ensure optimal quality of life. The literature has demonstrated that integrated care approaches are one key success factor for delivering person-centered and sustainable care for older people, with rehabilitation being a cornerstone in tertiary care prevention for older citizens. The current paper addresses the state of the literature for person-centered geriatric rehabilitation (GR) and the importance of personalized and participatory goal setting. In accordance with the bio–psycho–social model of the International Classification of Functioning, Disability and Health (ICF), social participation and the related goals are of particular importance for the entire rehabilitation process. The social participation of individuals enrolled into GR is therefore one of the milestones to be achieved during GR. Personalized goal setting during the entire rehabilitation process, Comprehensive Geriatric Assessment (CGA) and shared decision making allow a comprehensive care approach separate from solely function-based rehabilitation. The review also focusses on recent developments in digitalization in healthcare and delivers insights into how healthcare professionals’ collaborative practice supports sustainable rehabilitation results in patients of advanced chronological age. Full article

The biographical disruption that occurs in adolescents and young adults following a cancer diagnosis can affect various important psychosocial domains including relationships with family and friends, sexual development, vocational and educational trajectories, and physical and emotional wellbeing. While there is evidence of the physical impact of cancer during this period, less is known about the impact on emotional wellbeing and especially on the barriers for young people accessing help and support. We aimed to obtain a more in-depth understanding of young people’s experiences of their diagnosis, treatment, psychological impact, and range of resources they could or wanted to access for their mental health. We conducted an in-depth qualitative study using semi-structured interviews with 43 young people who had developed cancer aged 16 to 39 years and were either within 6 months of diagnosis or 3–5 years after treatment had ended. Framework analysis identified three themes: the emotional impact of cancer (expressed through anxiety, anger, and fear of recurrence); personal barriers to support through avoidance; and support to improve mental health through mental health services or adolescent and young adult treatment teams. We showed the barriers young people have to access care, particularly participant avoidance of support. Interrupting this process to better support young people and provide them with flexible, adaptable, consistent, long-term psychological support has the potential to improve their quality of life and wellbeing. Full article

Somatoform disorders (SD), commencing during adolescence, represent a major problem in health care systems. While literature underlines the high presence of mental health problems among children and adolescents afflicted by somatic symptoms in the general population, limited evidence is available on the prevalence of comorbid somatic symptoms in child and adolescent psychiatric populations. We assessed the prevalence of somatic symptoms, depression, and anxiety by validated questionnaires in an inpatient cohort. We further screened for the presence of SD. Out of 434 inpatients aged 11–17 years, 371 were included and a total of n = 288 (77.6%) children and adolescents participated in the study. A total of 93.8% of the inpatients reported somatic symptoms within the past six months and still almost half (45.7%) of the sample reported at least one somatic symptom within the last seven days prior to inquiry. Relating to the past six months, 59.5% were positively screened for SD, and 44.6% reported symptoms eligible for positive screening within the past seven days prior to the survey. Somatoform symptomatology was highly associated with anxiety and depression scores, but functional decline was amenable to the number of somatic symptoms only. We provide evidence that somatic symptoms are frequent in children and adolescents being treated in child and adolescent psychiatry and are relevant to everyday functioning. Screening for somatic symptoms should be introduced in the routine diagnostic procedures for early detection of SD in the commencing stages. Full article

Introducing Advanced Air Mobility (AAM) as a novel transportation mode poses unique challenges due to limited practical and empirical data. One of these challenges involves accurately estimating future passenger demand and the required number of air taxis, given uncertainties in modal shift dynamics, induced traffic patterns, and long-term price elasticity. In our study, we use mobility data obtained from a Dresden traffic survey and modal shift rates to estimate the demand for AAM air taxi operations for this regional use case. We organize these operations into an air taxi rotation schedule using a Mixed Integer Linear Programming (MILP) optimization model and set a tolerance for slight deviations from the requested arrival times for higher productivity. The resulting schedule aids in determining the AAM fleet size while accounting for flight performance, energy consumption, and battery charging requirements tailored to three distinct types of air taxi fleets. According to our case study, the methodology produces feasible and high-quality air taxi flight rotations within an efficient computational time of 1.5 h. The approach provides extensive insights into air taxi utilization, charging durations at various locations, and assists in fleet planning that adapts to varying, potentially uncertain, traffic demands. Our findings reveal an average productivity of 12 trips per day per air taxi, covering distances from 13 to 99 km. These outcomes contribute to a sustainable, business-focused implementation of AAM while highlighting the interaction between operational parameters and overall system performance and contributing to vertiport capacity considerations. Full article

Digital twins are among the technologies that are considered to have high potential. At the same time, there is no uniform understanding of what this technology means. Definitions are used across disciplinary boundaries, resulting in a multitude of different interpretations. The concepts behind the terms should be clearly named to transfer knowledge and bundle developments in digitalization. In particular, the Reference Architectural Model for Industry (RAMI) 4.0, as the guiding concept of digitalization, should be in harmony with the terms to be able to establish a contradiction-free relationship. This paper therefore summarizes the most important definitions and descriptions from the scientific community. By evaluating the relevant literature, a concept is derived. The concept presented in this work concretizes the requirements and understanding of digital twins in the frame of RAMI 4.0 with a focus on manufacturing. It thus contributes to the understanding of the technology. In this way, the concept is intended to contribute to the implementation of digital twins in this context. Full article

In recent years, the development of non-dairy probiotic beverages has been stimulated due to the increase in the number of people with milk protein allergies, lactose intolerance, and those that are vegetarian and vegan eating. These functional foods have a number of health benefits, combining properties of plant matrices and probiotic effects. However, a major challenge in formulating these beverages is the limited number of adapted microbial strains with probiotic phenotype that promote desirable sensory characteristics, besides remaining viable in the final product for long periods. Therefore, this review aimed to provide an overview of the production of traditional non-dairy fermented beverages produced in the world and to show the biotechnological potential of these foods as a source of strains presenting a probiotic phenotype. In addition, the latest developments on the role of lactic acid bacteria, Bifidobacterium, and yeast species in the development of new probiotic beverages from the fermentation of fruit and cereal are discussed. Finally, some aspects related to food safety issues are shown. Full article

The following paper examines the practicality of a methodical approach for energy-flexible and energy-optimal operation in the field of metal-cutting production. The analysis is based on the example of a grinding machine and its central cooling-supply system. In the first step, an energy-flexibility data model is built for each subsystem, which describes energy flexibility potentials generically. This is then extended to enable combined energy cost-optimal production planning. As a basis for the links between the data model representations, the cold flows between the subsystems are modeled using parameter-estimation methods, which have a mean absolute error of only 2.3 percent, making the subsequent installation of heat meters unnecessary. Based on the presented approach, the results successfully validate the possibility of energy-flexible cost-optimal and sensor-reduced production planning by reducing energy costs by 6.6 percent overall and 1.9 percent per workpiece produced. Full article

The metabotropic glutamate receptor 1 (mGlu₁) plays a pivotal role in synaptic transmission and neuronal plasticity. Despite the fact that several interacting proteins involved in the mGlu₁ subcellular trafficking and intracellular transduction mechanisms have been identified, the protein network associated with this receptor in specific brain areas remains largely unknown. To identify novel mGlu₁-associated protein complexes in the mouse cerebellum, we used an unbiased tissue-specific proteomic approach, namely co-immunoprecipitation followed by liquid chromatography/tandem mass spectrometry analysis. Many well-known protein complexes as well as novel interactors were identified, including G-proteins, Homer, δ2 glutamate receptor, 14-3-3 proteins, and Na/K-ATPases. A novel putative interactor, KCTD12, was further investigated. Reverse co-immunoprecipitation with anti-KCTD12 antibodies revealed mGlu₁ in wild-type but not in KCTD12-knock-out homogenates. Freeze-fracture replica immunogold labeling co-localization experiments showed that KCTD12 and mGlu₁ are present in the same nanodomain in Purkinje cell spines, although at a distance that suggests that this interaction is mediated through interposed proteins. Consistently, mGlu₁ could not be co-immunoprecipitated with KCTD12 from a recombinant mammalian cell line co-expressing the two proteins. The possibility that this interaction was mediated via GABA_B receptors was excluded by showing that mGlu₁ and KCTD12 still co-immunoprecipitated from GABA_B receptor knock-out tissue. In conclusion, this study identifies tissue-specific mGlu₁-associated protein clusters including KCTD12 at Purkinje cell synapses. Full article

Background: Surgery is the standard treatment in localized renal cell carcinoma (RCC). Pembrolizumab is now approved for adjuvant therapy in high-risk patients. However, inhomogeneity of studies gives ambiguity which patient benefit most from adjuvant therapy. A high infiltration of CD8⁺ T cells is known to be linked with poor prognosis in RCC. CXCR3 is a key player of CD8⁺ T cell differentiation and infiltration. We aimed to evaluate CXCR3 as a potential marker for predicting recurrence. Methods: CXCR3 and immune cell subsets (CD4, CD8, CD68 and FoXP3) were measured on RCC samples by multiplex immunofluorescence (mIF) staining. Cellular localization of CXCR3 was evaluated using single-cell RNA analysis on a publicly available dataset. Results: Tumor samples of 42 RCC patients were analyzed, from which 59.5% were classified as clear-cell RCC and of which 20 had recurrence. Single-cell RNA analysis revealed that CXCR3 was predominantly expressed in intratumoral T cells and dendritic cells. CXCR3 expression was higher in advanced tumors stages (p = 0.0044) and grade (p = 0.0518), correlating significantly with a higher CD8⁺ T cell expression (p < 0.001). Patients with CXCR3^high RCCs had also a significant shorter RFS compared to CXCR3^low (median: 78 vs. 147 months, p = 0.0213). In addition, also tumor stage pT3/4 (p < 0.0001) as well as grade G3/4 (p = 0.0008) negatively influenced RFS. Conclusion: CXCR3^high cell density was associated with high T cell infiltration and advanced tumor stage, worsening RFS in surgically resected RCC patients. Beside its prognostic value, CXCR3 might be a predictive biomarker to guide therapy decision for adjuvant therapy in localized RCC. Full article

Compositional alterations to high-entropy alloys (HEAs) allow further evolution of these materials by adjusting their property profiles. This way, they can be used for coating technologies and surface-protection applications. In the present work, minor quantities of the non-metallic alloying constituents, BSiC, were added to the CrFeNi base system. The alloy development was carried out in an electric arc furnace in comparison with the nickel-based alloy Ni-600. With regard to the BSiC-free variant, the wear resistance can be significantly increased. The powder was manufactured by inert gas atomization and characterized, followed by processing via high-velocity oxy-fuel spraying (HVOF) and high velocity laser metal deposition (HS-LMD). Depending on the manufacturing conditions, the proportion and shape of the precipitates within the microstructure differ. Compared to both the reference system and the as-cast condition, the coating systems demonstrated comparable or improved resistance to wear. The evaluation of the process–structure–property relationships confirmed the great potential of developing load-adapted HEA systems using non-metallic alloy constituents in the field of surface engineering. Full article

The use of yeasts as starter cultures was boosted with the emergence of large-scale fermentations in the 20th century. Since then, Saccharomyces cerevisiae has been the most common and widely used microorganism in the food industry. However, Candida species have also been used as an adjuvant in cheese production or as starters for coffee, cocoa, vegetable, meat, beer, and wine fermentations. A thorough screening of candidate Candida is sometimes performed to obtain the best performing strains to enhance specific features. Some commonly selected species include C. pulcherrima (teleomorph Metschnikowia pulcherrima) (wine), C. parapsilosis (teleomorph Monilia parapsilosis) (coffee), C. famata (teleomorph Debaryomyces hansenii) (cheese), and C. zeylanoides (teleomorph Kurtzmaniella zeylanoides) and C. norvegensis (teleomorph Pichia norvegensis) (cocoa). These species are associated with the production of key metabolites (food aroma formation) and different enzymes. However, safety-associated selection criteria are often neglected. It is widely known that some Candida species are opportunistic human pathogens, with important clinical relevance. Here, the physiology and metabolism of Candida species are addressed, initially emphasizing their clinical aspects and potential pathogenicity. Then, Candida species used in food fermentations and their functional roles are reported. We recommended that Candida not be used as food cultures if safety assessments are not performed. Some safety features are highlighted to help researchers choose methods and selection criteria. Full article

Over the past years, NGS has become a crucial workhorse for open-view pathogen diagnostics. Yet, long turnaround times result from using massively parallel high-throughput technologies as the analysis can only be performed after sequencing has finished. The interpretation of results can further be challenged by contaminations, clinically irrelevant sequences, and the sheer amount and complexity of the data. We implemented PathoLive, a real-time diagnostics pipeline for the detection of pathogens from clinical samples hours before sequencing has finished. Based on real-time alignment with HiLive2, mappings are scored with respect to common contaminations, low-entropy areas, and sequences of widespread, non-pathogenic organisms. The results are visualized using an interactive taxonomic tree that provides an easily interpretable overview of the relevance of hits. For a human plasma sample that was spiked in vitro with six pathogenic viruses, all agents were clearly detected after only 40 of 200 sequencing cycles. For a real-world sample from Sudan, the results correctly indicated the presence of Crimean-Congo hemorrhagic fever virus. In a second real-world dataset from the 2019 SARS-CoV-2 outbreak in Wuhan, we found the presence of a SARS coronavirus as the most relevant hit without the novel virus reference genome being included in the database. For all samples, clinically irrelevant hits were correctly de-emphasized. Our approach is valuable to obtain fast and accurate NGS-based pathogen identifications and correctly prioritize and visualize them based on their clinical significance: PathoLive is open source and available on GitLab and BioConda. Full article