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Climatic Influence on Growth Performance of Abies spectabilis in the Himalayas
Get PDFClimate change has affected forest ecosystems across the world over the past century. However, its impact is particularly high in the Himalayas due to increasing temperatures, extreme precipitation events, and regional droughts. In this context, a review of the current stage of research was deemed necessary to understand the adaptation of a key conifer species to climate variability in the Central Himalayas. Hence, we conducted a systematic review of published peer-reviewed journal articles addressing the growth performance of Abies spectabilis (D. Don) Spach in the Central Himalayas. From this review, three main patterns of climate response have emerged: a positive correlation of radial tree growth with temperature of the current and previous growing seasons, tree growth limitation by winter temperature, and by temperature or moisture in the pre-monsoon season. Overall, results indicate an elevation-dependent temperature sensitivity, a crucial role of moisture availability, and seasonal shifts in climate–growth relationships, reflecting the species’ adaptability to changing climate conditions. Our review revealed that studies on elevation-dependent adaptation of wood anatomical traits by A. spectabilis are still rare. The tree-ring growth of this species shows a complex response to climate variability, with increasing as well as decreasing growth trends across its distribution range.This work was supported by the Open-Access Publishing Fund provided by the Free University of Bozen-Bolzano.Open-Access Publishing Fun
Characterisation of Mesenchymal Stromal Cells (MSCs) from Human Adult Thymus as a Potential Cell Source for Regenerative Medicine
Get PDFBackground: Mesenchymal stem cell-based therapy may be indicated in ischaemic heart disease. The use of autologous adipose-derived mesenchymal stromal cells (AdMSCs) offers regenerative potential due to their paracrine effects. The aim of this study was to expand and characterise adult human thymus-derived MSCs harvested during open heart surgery with respect to their stem cell and paracrine properties. Methods : Enzymatically and non-enzymatically isolated human thymic AdMSCs (ThyAdMSCs) were cultured in xeno-free media containing pooled human platelet lysate (pPL). MSC characterisation was performed. Ex vivo expanded ThyAdMSCs were differentiated into three lineages. Proliferative capacity and immunomodulatory properties were assessed by proliferation assays and mixed lymphocyte reaction, respectively. Gene expression analysis was performed by qPCR. Results: Both isolation methods yielded fibroblast-like cells with plastic adherence and high proliferation. Flow cytometry revealed distinct expression of MSC markers in the absence of haematopoietic cell surface markers. Ex vivo expanded ThyAdMSCs could be differentiated into adipocytes, osteocytes, and chondrocytes. Activated peripheral blood mononuclear cells were significantly reduced when co-cultured with ThyAdMSCs, indicating their ability to inhibit immune cells in vitro. Gene expression analysis showed significantly less IFNγ and TNFα, indicating an alteration of the activated and pro-inflammatory state in the presence of ThyAdMSCs. Conclusions : These results demonstrate an efficient method to generate AdMSCs from human thymus. These MSCs have a strong immunomodulatory capacity and are, therefore, a promising cell source for regenerative medicine. The culture conditions are crucial for cells to proliferate in culture. Further research could explore the use of ThyAdMSCs or their secretome in surgical procedures.This research received not external funding
The impact of competition mode and verbal encouragement on physiological, physical, and technical performances in youth football
Get PDFThe present study compared the physiological, physical, and technical performances during “FUNino” (3 vs. 3) to that of the standard competition mode (7 vs. 7) under the influence of two coaching feedback situations (verbal encouragement vs. no verbal encouragement). “FUNino” features a 3-a-side game on a small pitch size (20 × 27-meter) with specific scoring rules (scoring within a 6 m goal zone) utilizing four small goals played without goalkeeper. There are also no offsides or throw-ins, however a kick- or dribble in. Sixteen U11 male youth footballers performed eight 10-min games, four in the “FUNino” and four in the standard competition game (7 vs. 7) in accordance to the German national government soccer association (DFB). All games were videotaped and physiological, physical, and technical parameters quantified for each game. A two-factors linear model with repeated measurement (ANOVA) were used to analyze the parameters. There were significant (p < 0.05) higher physiological (+7.10%), physical (+17.3%), and technical (+219%) parameters in the “FUNino” format. There were also significant higher physical (average (+8.88%) and relative (+5.47%) running distance) as well as technical (relative number of ball touches, + 9.69%) parameters in the feedback mode. “FUNino” provided a significant higher number of physiological, physical, and technical demands than the 7 vs. 7 used by the national soccer government association. Additionally, verbal encouragement positively influenced running distance. Competition format had greater influence on physiological, physical, and technical outcome compared to verbal encouragement
ESR Essentials: how to get to valuable radiology AI: the role of early health technology assessment—practice recommendations by the European Society of Medical Imaging Informatics
Get PDFAI tools in radiology are revolutionising the diagnosis, evaluation, and management of patients. However, there is a major gap between the large number of developed AI tools and those translated into daily clinical practice, which can be primarily attributed to limited usefulness and trust in current AI tools. Instead of technically driven development, little effort has been put into value-based development to ensure AI tools will have a clinically relevant impact on patient care. An iterative comprehensive value evaluation process covering the complete AI tool lifecycle should be part of radiology AI development. For value assessment of health technologies, health technology assessment (HTA) is an extensively used and comprehensive method. While most aspects of value covered by HTA apply to radiology AI, additional aspects, including transparency, explainability, and robustness, are unique to radiology AI and crucial in its value assessment. Additionally, value assessment should already be included early in the design stage to determine the potential impact and subsequent requirements of the AI tool. Such early assessment should be systematic, transparent, and practical to ensure all stakeholders and value aspects are considered. Hence, early value-based development by incorporating early HTA will lead to more valuable AI tools and thus facilitate translation to clinical practice. Clinical relevance statement This paper advocates for the use of early value-based assessments. These assessments promote a comprehensive evaluation on how an AI tool in development can provide value in clinical practice and thus help improve the quality of these tools and the clinical process they support. Key Points Value in radiology AI should be perceived as a comprehensive term including health technology assessment domains and AI-specific domains. Incorporation of an early health technology assessment for radiology AI during development will lead to more valuable radiology AI tools. Comprehensive and transparent value assessment of radiology AI tools is essential for their widespread adoption
Chemoradiation-Altered Micromilieu of Glioblastoma Cells Particularly Impacts M1-like Macrophage Activation
Get PDFGlioblastoma is a highly aggressive brain tumor with an overall poor prognosis due to its immunosuppressive tumor microenvironment (TME). Microglia and tumor-associated macrophages (TAMs) with pro-tumorigenic properties are dominant populations of immune cells in the glioblastoma TME. To date, several studies targeting TAMs to fight tumor progression in different tumor entities have been initiated. However, the impact of standard therapy schemes of glioblastoma cells on macrophage polarization, activation, and phagocytosis remains controversial. The same applies to the relevance of PD-1/PD-L1 blockade in the interaction between macrophages and tumor cells. Our study, therefore, investigated patient-oriented treatment of GLIOBLASTOMA by examining the phagocytic capacity of polarized M1- and M2-like macrophages using GL261-luc2 tumor cells as a preclinical model system. Additionally, we analyzed the expression of activation and immune checkpoint markers on these macrophage subtypes following contact with tumor cells and their microenvironment. These factors were also determined after PD-1 blockade was initiated. The analyses revealed that the immunoregulatory M2-like macrophages generally exhibited a higher phagocytosis rate than the pro-inflammatory M1-like macrophages; however, this was not influenced by the pretreatment of glioblastoma cells with chemo- or radiotherapy. This could not be improved by blocking the PD-1 receptor. Furthermore, there were no modulations in the expression of differentiation, activation, or immune checkpoint molecules of M1- and M2-like macrophages after cell-to-cell contact with glioblastoma cells. But the medium conditioned by tumor cells strongly altered M1-like macrophages toward a more activated state, whereas M2-like cells were only mildly influenced. This was further enhanced by tumor cell treatment, with the most prominent effect after irradiation. These results suggest that conventional GLIOBLASTOMA tumor cell treatment affects the immunogenic status of macrophage subtypes, which is relevant for enhancing the anti-tumor immune response in brain tumors.This research was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, grant number DE 2503/2-1).Deutsche Forschungsgemeinschaf
Overweight and Obesity in Adults with Congenital Heart Disease and Heart Failure: Real-World Evidence from the PATHFINDER-CHD Registry †
Get PDFBackground: The PATHFINDER-CHD Registry is a prospective, multicenter, non-interventional registry across tertiary care centers in Germany. The aim is to analyze real-world data on adults with congenital heart defects (ACHD) or hereditary connective tissue disorders who have manifest heart failure (HF), a history of HF, or are at significant risk of developing HF. This analysis investigates the prevalence and clinical impact of overweight and obesity in this unique population. Methods: As of 1st February, 2025, a total of 1490 ACHD had been enrolled. The mean age was 39.4 ± 12.4 years, and 47.9% were female. Patients were categorized according to Perloff’s functional class and the Munich Heart Failure Classification for Congenital Heart Disease (MUC-HF-Class). Results: The most common congenital heart disease (CHD) in this cohort was Tetralogy of Fallot, transposition of the great arteries, and congenital aortic valve disease. Marfan syndrome was the most common hereditary connective tissue disease. Of the patients, 46.1% were classified as overweight (32.8%) or obese (13.3%), while 4.8% were underweight. The highest prevalence of overweight (47.1%) was observed among patients who had undergone palliative surgery, whereas untreated patients showed the highest proportion of normal weight (57.2%). Cyanotic patients were predominantly of normal weight. Patients with univentricular circulation exhibited significantly lower rates of overweight and obesity (35%; p = 0.001). Overweight and obesity were statistically significantly associated with arterial hypertension, diabetes mellitus, and sleep apnea (all p < 0.001). High BMI was linked to increased use of HF-specific medications, including SGLT2 inhibitors ( p = 0.040), diuretics ( p = 0.014), and angiotensin receptor blockers ( p = 0.005). Conclusions: The data highlight the clinical relevance of overweight and obesity in ACHD with HF, emphasizing the need for individualized prevention and treatment strategies. The registry serves as a critical foundation for the optimization of long-term care in this population.This work was supported by the German Heart Foundation (“Deutsche Herzstiftung e.V.”), the patient organization “Herzkind e.V.”, the “Förderverein Deutsches Herzzentrum München e.V.”, and “Gesellschaft für Prävention e.V. (GPeV)”.German Heart Foundation (“Deutsche Herzstiftung e.V.”)“Herzkind e.V.”“Förderverein Deutsches Herzzentrum München e.V.”“Gesellschaft für Prävention e.V. (GPeV)
Die Bewertung der Institutionen der wirtschaftlichen Freiheit in der Autonomen Region Kurdistan im Irak (KRI)
Get PDFAbstract
This dissertation investigates the institutional foundations of economic freedom in the Kurdistan Region of Iraq (KRI), offering a comprehensive evaluation of both governmental and private-order institutions in the context of federalism, the transition to a free market, and political and social diversity. Drawing on the theoretical framework of classical liberalism and institutional economics—particularly the distinction between coercive and non-coercive state activities—it aims to determine the extent to which institutions in KRI are compatible with the principles of individual economic freedom.
The study adopts a qualitative methodological approach rooted in institutional analysis, examining legal texts, policy documents, field interviews, and secondary data. It classifies governmental activities into three categories: freedom-compatible coercive (e.g., protection of property rights, contract enforcement, coersion protection), freedom-incompatible coercive (e.g., subsidies, politically motivated control of public enterprises), and non-coercive (e.g., infrastructure, monetary stability, information and social services). Private-order institutions, such as tribal structures, religious norms, and informal dispute resolution mechanisms, are also evaluated for their substitutive and complementary roles in governance and market operations.
Findings reveal that the institutions of economic freedom in KRI are only partially developed and often conflict with economic freedom principles as they deviate from the rule of law. Governmental institutions are plagued by legal uncertainty, politicization of the judiciary, weak protection of property rights and contract enforcement, corruption, and the dominance of ruling parties (e.g. KDP and PUK) over state functions. These deficiencies undermine the rule of law, distort market incentives, and concentrate economic power. Meanwhile, private-order institutions provide adaptive solutions in the absence of effective state structures, but they remain informal, fragmented, and prone to social bias.
The study concludes that the institutional environment in KRI suffers from a dual crisis: govermental institutions fail to act as neutral enforcers of general rules, while non-governmental institutions, although flexible, cannot guarantee predictability or equal access. The dissertation recommends constitutional reforms to reduce party dominance, strengthen the rule of law, depoliticize security and judicial bodies, empower independent oversight institutions, and foster a legal framework that supports voluntary exchange and secure property rights. By bridging the gap between normative institutional theory and empirical subnational analysis, the research contributes to debates on institutional development, economic freedom, and governance reform in transitional societies
Visual perception and cognitive functioning in MCI and mild Alzheimer’s disease: a cross-sectional study protocol from the DEM-VIS study in Germany
Get PDFIntroduction Visual perception is a fundamental skill that plays a central role in sensing the external environment. Deficits can lead to impairments in everyday activities. Visual perception is known to be impaired in Alzheimer’s disease (AD). However, the extent to which visual perception is impaired in mild cognitive impairment (MCI), often a prodromal state of AD, has not been sufficiently investigated. This study aims to assess visual perceptual abilities in people with MCI and mild AD compared with healthy controls. It will also investigate whether executive functions, activities of daily living and intelligence are affected in this context, providing new insights into the research of visual perception together with MCI and mild AD. Methods and analysis People with MCI, mild AD and healthy controls will be assessed for cognitive deficits using the Syndrom-Kurztest (SKT). Visual perceptual performance will be assessed using the German version of the Developmental Test of Visual Perception-Adolescent and Adult: Second Edition (DTVP-A:2; Frostings Entwicklungstest der visuellen Wahrnehmung – Jugendliche und Erwachsene 2. Auflage). Activities of daily living will be assessed through the Erlangen Test of Activities of Daily Living in Persons with Mild Dementia or Mild Cognitive Impairment (ETAM) and the Bayer Activities of Daily Living Scale (B-ADL). Executive functions will be measured using the German adaptation of the Behaviour Rating Inventory of Executive Function - Adult (BRIEF-A) and intelligence will be assessed using the Matrix Reasoning and Vocabulary Test of the Wechsler Adult Intelligence Scale - Fourth Edition (WAIS-IV). Data analysis will involve descriptive analyses, linear regression analyses, multivariate analysis of variance, mediation analysis and structural equation modelling. Ethics and dissemination This study has received approval from the Ethics Committee of Helmut Schmidt University/University of the Federal Armed Forces Hamburg, Germany (number: 2023_009). Findings will be disseminated through peer-reviewed publications and presentations at national and international conferences. Trial registration number Registered at OSF https://doi.org/10.17605/OSF.IO/PM5A
Topology and Material Optimization of Optical Properties of Particulate Products
No full textIn recent years, the design of electromagnetic scattering objects with respect to their optical properties has become an interesting field of research and represents one of the main focuses within nanoparticle technology. In particular, there has been a notable increase in interest in the topology and the more generalized material optimization of individual particles and specially arranged assemblies of nanoparticles. These particulate products exhibit intriguing optical properties, which render them attractive for applications in a wide range of research fields.
In this work, we predict the electromagnetic scattering behaviour, which is described by the Maxwell’s equations in time-harmonic form, of a range of objects. The solution to this system is approximated by either the discrete dipole approximation (DDA) or transition matrix method (TMM). While in DDA the whole scattering object is discretized into individual cells called dipoles, in TMM the electromagnetic fields of each constituent in the system are expanded in terms of vector spherical wave functions. Therefore, DDA is ideal for predicting scattering properties of arbitrarily shaped individual nanoparticles and small particle clusters, while TMM is also applicable to larger particle assemblies where the individual components may be more distant from each other.
In order to compute an improved design in terms of an optical property function, we consider a design optimization approach in which either DDA or TMM is employed to approximate the solution of the time-harmonic Maxwell’s system. The fundamental aspect of the optimization approach is the iterative assignment of a material property from a pre-defined catalogue of admissible materials to each component of the system until a local minimum of the chosen objective function is reached. In the DDA setting, the material property of each dipole is changed, whereas in the TMM framework, the material property of each nanoparticle within the system itself is modified. The design updates are calculated by applying a separable model of the original optimization objective function, which allows the solution of the resulting optimization subproblem to global optimality and thus gives rise to a sequential global programming (SGP) algorithm.
We propose various types of separable models, including exact separable models, which remain fully accurate as long as a single design variable is modified. Furthermore, we suggest the use of tight separable approximations of the aforementioned models, which offer a straightforward computational tractability. We demonstrate the strength and efficacy of the DDA-SGP and TMM-SGP approach for an academic proof-of-concept example and apply these methods to address different problems in nanoparticle technology. The application of DDA allows for a significantly higher design resolution than that achievable with finite element based methods. Moreover, the efficiency and accuracy of TMM permits the consideration also of large particle clusters. The combination of these two approaches with structural design algorithms expands the range of numerically tractable and feasible design problems concerning photonic nanostructures and their optical applications
Marine-Inspired Ovothiol Analogs Inhibit Membrane-Bound Gamma-Glutamyl-Transpeptidase and Modulate Reactive Oxygen Species and Glutathione Levels in Human Leukemic Cells
Get PDFThe enzyme γ-glutamyl transpeptidase (GGT), located on the surface of cellular membranes, hydrolyzes extracellular glutathione (GSH) to guarantee the recycling of cysteine and maintain intracellular redox homeostasis. High expression levels of GGT on tumor cells are associated with increased cell proliferation and resistance against chemotherapy. Therefore, GGT inhibitors have potential as adjuvants in treating GGT-positive tumors; however, most have been abandoned during clinical trials due to toxicity. Recent studies indicate marine-derived ovothiols as more potent non-competitive GGT inhibitors, inducing a mixed cell-death phenotype of apoptosis and autophagy in GGT-overexpressing cell lines, such as the chronic B leukemic cell HG-3, while displaying no toxicity towards non-proliferative cells. In this work, we characterize the activity of two synthetic ovothiol analogs, L-5-sulfanylhistidine and iso-ovothiol A, in GGT-positive cells, such as HG-3 and HL-60 cells derived from acute promyelocytic leukemia. The two compounds inhibit the activity of membrane-bound GGT, without altering cell vitality nor inducing cytotoxic autophagy in HG-3 cells. We provide evidence that a portion of L-5-sulfanylhistidine enters HG-3 cells and acts as a redox regulator, contributing to the increase in intracellular GSH. On the other hand, ovothiol A, which is mostly sequestered by external membrane-bound GGT, induces intracellular ROS increase and the consequent autophagic pathways. These findings provide the basis for developing ovothiol derivatives as adjuvants in treating GGT-positive tumors’ chemoresistance.A.Z. has been supported by a fellowship funded by a Next-Generation EU_ PRIN 2022 Grant awarded by the Italian Ministry of University Research, no. 2022MJBEK9, CUP E53D23009970006.Italian Ministry of Universi