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Thermoplasmonic Manipulation for the Study of Single Polymers and Protein Aggregates
No full textHeat generation by means of plasmonic structures, which is at the heart of
thermoplasmonics, has stimulated intense research on the manipulation of
matter in liquid environments. Tiny noble metal structures with dimensions of
a few tens of nanometers thereby serve as heat sources generating large
temperature gradients. As a result, thermophoretic drifts occur, concentration
fields form, or charge separation takes place. But also hydrodynamic
boundary flows, which play an important role in microfluidic environments,
can be induced. These processes remotely triggered by optically generated
local dynamic temperature fields offer novel possibilities for manipulating and
studying not only colloids but in particular also single molecules and their
aggregates in solution
Vesicular Release and Uptake of Circular LSD1-RNAs from Non-Cancer and Cancer Lung Cells
No full textLysine-specific demethylase 1 (LSD1) is highly expressed in many cancer types and strongly associated with cancer progression and metastasis. Circular RNAs (circRNAs) are produced by back-splicing and influence the interactive RNA network by microRNA and protein sponging. In the present study, we aimedto identify circRNAs that derive from the LSD1-encoding KDM1A gene, and to investigate their potential to be released and uptaken by lung cancer versus non-cancer epithelial cells. We identified four circLSD1-RNAs by RT-PCR with divergent primers, followed by sequencing. The expression level of circLSD1-RNAs was then studied by quantitative PCR on cellular and extracellular fractions of lung cancer (PC9) and non-cancer primary small airway epithelial (PSAE) cells. Moreover, we established the transgenic overexpression of circLSD1-RNAs. We show that circLSD1-RNAs are primarily located in the cytoplasm, but are packaged and released from lung cancer and non-cancer cells by extracellular vesicles (EVs) and ribonucleoprotein (RNP) complexes, respectively. Proteomics demonstrated a different protein pattern of EV fractions released from PC9 versus PSAE cells. Importantly, released circLSD1-RNAs were differently taken up by PSAE and PC9 cells. In conclusion, our findings provide primary evidence that circLSD1-RNAs participate in the intercellular communication of lung cancer cells with the tumor environment
Who benefits most from outpatient lifestyle intervention?: An IMI-SOPHIA study on pediatric individuals living with overweight and obesity
No full textObjective
The first-line approach for childhood obesity is lifestyle intervention (LI); however, success varies. This study aimed first to identify distinct subgroups of response in children living with overweight and obesity and second to elucidate predictors for subclusters.
Methods
Based on the obesity patient follow-up registry the APV (Adipositas-Patienten-Verlaufsdokumentation) initiative, a total of 12,453 children and adolescents (median age: 11.5 [IQR: 9.7–13.2] years; BMI z score [BMIz]: 2.06 [IQR: 1.79–2.34]; 52.6% girls) living with overweight/obesity and participating in outpatient LI were studied. Longitudinal k-means clustering was used to identify individual BMIz response curve for up to 2 years after treatment initiation. Multinomial logistic regression was used to elucidate predictors for cluster membership.
Results
A total of 36.3% of children and adolescents experienced “no BMIz loss.” The largest subcluster (44.8%) achieved “moderate BMIz loss,” with an average delta-BMIz of −0.23 (IQR: −0.33 to −0.14) at study end. A total of 18.9% had a “pronounced BMIz loss” up to −0.61 (IQR: −0.76 to −0.49). Younger age and lower BMIz at LI initiation, larger initial BMIz loss, and less social deprivation were linked with higher likelihood for moderate or pronounced BMIz loss compared with the no BMIz loss cluster (all p < 0.05).
Conclusions
These results support the importance of patient-tailored intervention and earlier treatment escalation in high-risk individuals who have little chance of success
Analytical Validation of an Immunohistochemical 7-Biomarker Prognostic Assay (immunoprint®) for Early-Stage Cutaneous Melanoma in Archival Tissue of Patients with AJCC v8 T2–T3 Disease
No full textSelected patients with early-stage melanoma have a “hidden high risk” of poor oncologic outcomes. They might benefit from clinical trials, and ultimately, if warranted by trial results, judicious everyday use of adjuvant therapy. A promising tool to identify these individuals is the immunoprint® assay. This immunohistochemical 7-biomarker prognostic test was clinically validated in three independent cohorts (N = 762) to classify early-stage patients as high-risk or low-risk regarding melanoma recurrence and mortality. Using College of American Pathologists (CAP) recommendations, we analytically validated this assay in primary melanoma specimens (N = 20 patients). We assessed assay precision by determining consistency of risk classification under repeated identical conditions (repeatability) or across varying conditions (reproducibility), involving separate assay runs, operators (laboratory scientists), and/or observers (e.g., dermatopathologists). Reference classification was followed by five analytical validation phases: intra-run/intra-operator, intra-observer, inter-run, inter-operator, and inter-observer. Concordance of classifications in each phase was assessed via Fleiss’ kappa (primary endpoint) and percent agreement (secondary endpoint). Seven-marker signature classification demonstrated high consistency across validation categories (Fleiss’ kappa 0.864–1.000; overall percent agreement 95–100%), in 9/10 cases, exceeding, and in 1/10 cases, closely approaching, CAP’s recommended 0.9 level. The 7-marker assay has now been verified to provide excellent repeatability, reproducibility, and precision, besides having been clinically validated
Molybdenum-Mediated Insertion of Ketones into the P−P bond of cyclo-(P5Ph5) and Formation of Trinuclear Molybdenum Complexes
No full textThe reaction of cyclopentaphosphine cyclo-(P5Ph5) (1) with ketones (acetone and cyclooctanone) in the presence of [Mo(CO)4(cod)] (cod=cycloocta-1,5-diene) led to air-stable trinuclear complexes in which the bis-phosphanido ligands (PPh−PPh−PPh−PPh−CMe2O−PPh)2− (complex 2) and (PPh−PPh−PPh−PPh−C(CH2)7O−PPh)2− (complex 3) bridge a Mo(CO)3−Mo(CO)3 unit. This extends the reaction of 1 with transition metal carbonyl complexes to further substrates and represents the first examples of insertion of carbonyl compounds into the P−P bond of cyclic oligophosphorus compounds. Complexes 2 and 3 have been characterized by 31P NMR spectroscopy and single crystal X-ray diffraction. Furthermore, the thermal properties of the obtained complexes have been studied by differential scanning calorimetry (DSC) and fast scanning calorimetry (FSC)
Interactive Visualization within the Reality-Virtuality Continuum to Support Motor Skill Learning and Education
No full textThis thesis investigates how interactive visualization techniques across Milgram's reality-virtuality continuum can enhance learning, focusing on both conceptual education and motor skill acquisition. Grounded in theories of experiential, skill-based, and situated learning, it establishes how interaction and immersion can create meaningful learning experiences in Mixed Reality (MR).
First, the work introduces a holistic educational framework for teaching complex concepts in an academic environment, specifically within computer graphics. The framework integrates interactive web applications, lecture slides, and quizzes. In a split-test experiment with 19 students, one group reviewed material via conventional slides, while the other used an interactive web application. Quiz results before and after repetition showed that the interactive group improved more strongly. Feedback from a UX expert and teaching staff was also consistently positive, highlighting the framework's usability and accessibility.
The thesis then narrows its focus to motor skill learning, a domain requiring the communication of intricate spatial and temporal information. A comprehensive literature review (2016–present) identifies 39 relevant studies on visual feedback in MR. These works are classified by feedback type, technology, and cue characteristics, revealing trends and gaps—particularly regarding understanding and applying visual cues such as superimposed human avatars.
To address these gaps, the thesis develops a framework for registering superimposed avatars, ensuring accurate spatial alignment for meaningful corrective feedback. Example exercises show how environmental anchoring improves a learner's interpretation of target movements.
Building on this, a real-time viewpoint-selection method is introduced. It dynamically adjusts the camera to balance pose clarity and feedback visibility, highlighting movement discrepancies through optimized visual cues. In a user study with 39 participants comparing four video variants, the new method was most frequently rated as the most informative. It also outperformed prior approaches computationally and was the only method capable of real-time operation.
The final contribution is a novel Augmented Reality (AR) feedback system that delivers motor-learning cues independently of the user's head orientation. By carefully positioning virtual feedback to maximize comfort and minimize distraction, the system supports correct exercise execution while preserving freedom of movement. In an in-subject study with 32 participants, the system was evaluated against conventional feedback methods. No disadvantages were found regarding accuracy or task completion time, and participants reported greater comfort and more positive overall experiences. They also identified movement errors more frequently, indicating improved interpretability.
Across academic and athletic contexts, the thesis demonstrates multiple innovative approaches for teaching complex concepts through interactive visualization in MR. It shows how tailored visual support, grounded in learning theory and optimized through user-centered design, can enrich understanding and enhance performance within the reality-virtuality continuum
Detection of Antibodies against Endemic and SARS-CoV-2 Coronaviruses with Short Peptide Epitopes
No full text(1) Background: Coronavirus proteins are quite conserved amongst endemic strains (eCoV) and SARS-CoV-2. We aimed to evaluate whether peptide epitopes might serve as useful diagnostic biomarkers to stratify previous infections and COVID-19. (2) Methods: Peptide epitopes were identified at an amino acid resolution that applied a novel statistical approach to generate data sets of potential antibody binding peptides. (3) Results: Data sets from more than 120 COVID-19 or eCoV-infected patients, as well as vaccinated persons, have been used to generate data sets that have been used to search in silico for potential epitopes in proteins of SARS-CoV-2 and eCoV. Peptide epitopes were validated with >300 serum samples in synthetic peptide micro arrays and epitopes specific for different viruses, in addition to the identified cross reactive epitopes. (4) Conclusions: Most patients develop antibodies against non-structural proteins, which are useful general markers for recent infections. However, there are differences in the epitope patterns of COVID-19, and eCoV, and the S-protein vaccine, which can only be explained by a high degree of cross-reactivity between the viruses, a pre-existing immune response against some epitopes, and even an alternate processing of the vaccine proteins
Potential sex differences in human milk fatty acids and their association with atopic dermatitis: Results of the Ulm SPATZ health study
No full textBackground: Polyunsaturated fatty acids (PUFAs) in human milk are essential in immune
system maturation and might play a role in the development of allergic conditions,
such as atopic dermatitis (AD) in infants. Immune system responses are
modulated by sex, but data on the sex-specific
associations with PUFAs are limited.
We therefore explored sex-specific
differences in human milk PUFAs and their association
with AD up to 2 years.
Methods: PUFAs were measured in human milk samples from the Ulm SPATZ Health
Study at 6 weeks (n = 512) and 6 months (n = 367). Associations with AD up to 2 years
were evaluated using crude and multivariable logistic regression. Interactions between
infant sex and PUFAs were explored by including the product term.
Results: No significant associations were observed with 6-week
data. At 6 months, the
median relative proportion of docosahexaenoic acid (DHA) was significantly higher in
milk for female than male infants (p = .001). Female infants whose milk was lower in
quintile proportions of alpha-linolenic
acid (ALA) at 6 months had lower odds of AD
compared to males [first vs. fifth quintile OR (95% confidence interval): 0.13 (0.02,
0.66), p = .02]. This interaction was not significant when correcting for multiple testing
(α threshold: p = .004). No other statistically significant associations were observed.
Conclusion: Individual quintile PUFA proportions in human milk were not associated
with AD, overall and in a sex-specific
manner. More comprehensive and statistically
powered longitudinal studies are needed to determine whether potential sex differences
in human milk, if any, could be of clinical relevance for infants including the
investigation of mediating factors
Association between TGFβ1 Levels in Cord Blood and Weight Progress in the First Year of Life
No full textTransforming growth factor beta-1 (TGFβ1) is an adipokine secreted from adipose tissue, placental tissue and immune cells with a role in cell proliferation, cell apoptosis and angiogenic proliferation. The role of TGFβ1 in pregnancy and child growth and the source of cord TGFβ1 are yet unknown. In this study, we sought to clarify the correlation of TGFβ1 levels with parameters of intrauterine growth and child growth during the first year of life, and to determine whether their source is primarily of fetal or maternal origin. Serum samples and anthropometric measurements were obtained from the LIFE Child cohort of 79 healthy mother–child pairs. Measurements were conducted using enzyme-linked immunosorbent assays. Statistical analyses including Mann–Whitney U-test, correlation analyses and linear regression analyses were performed using GraphPad Prism and R. TGFβ1 levels were significantly higher in cord than in maternal serum, suggesting a fetal origin. Multivariate regression analyses revealed strong positive associations between cord TGFβ1 levels at birth and child weight at U6. Furthermore, cord TGFβ1 was significantly correlated with child weight at approximately one year of age. An increase of 10,000 pg/mL in cord TGFβ1 concentrations at birth was associated with a higher body weight of 201 g at roughly one year of age when adjusted for sex
Assessing Osteolytic Lesion Size on Sequential CT Scans Is a Reliable Study Endpoint for Bone Remineralization in Newly Diagnosed Multiple Myeloma
No full textMultiple myeloma (MM) frequently induces persisting osteolytic manifestations despite hematologic treatment response. This study aimed to establish a biometrically valid study endpoint for bone remineralization through quantitative and qualitative analyses in sequential CT scans. Twenty patients (seven women, 58 ± 8 years) with newly diagnosed MM received standardized induction therapy comprising the anti-SLAMF7 antibody elotuzumab, carfilzomib, lenalidomide, and dexamethasone (E-KRd). All patients underwent whole-body low-dose CT scans before and after six cycles of E-KRd. Two radiologists independently recorded osteolytic lesion sizes, as well as the presence of cortical destruction, pathologic fractures, rim and trabecular sclerosis. Bland–Altman analyses and Krippendorff’s α were employed to assess inter-reader reliability, which was high for lesion size measurement (standard error 1.2 mm) and all qualitative criteria assessed (α ≥ 0.74). After six cycles of E-KRd induction, osteolytic lesion size decreased by 22% (p < 0.001). While lesion size response did not correlate with the initial lesion size at baseline imaging (Pearson’s r = 0.144), logistic regression analysis revealed that the majority of responding osteolyses exhibited trabecular sclerosis (p < 0.001). The sum of osteolytic lesion sizes on sequential CT scans defines a reliable study endpoint to characterize bone remineralization. Patient level response is strongly associated with the presence of trabecular sclerosis