Search Results (1,633)

Lipofilling has far more applications than cosmetic surgery alone. Due to its high content of stromal vascular fraction (SVF) cells, lipoaspirate can also be used to treat wounds, as its cellular components may accelerate wound healing. Using our CELT^PLUS protocol, we can increase the number of SVF cells per volume. Unfortunately, some patients require more than one treatment to achieve an optimal outcome, but would unnecessarily suffer from repeated liposuction. Therefore, our objective was to test whether cryopreserving CELT^PLUS fat could offer a solution, potentially avoiding the need for repeated liposuction procedures. DMSO was used as a cryoprotective agent for proof-of-principle testing, although other non-toxic cryoprotective agents should be considered in the future. The rest of our freezing protocol is a clinically friendly attempt to facilitate the translation into clinical practice. We tested the cryopreserved tissue using histological evaluation, metabolism measurement, SVF cell yield estimation, PCRs from both whole tissue and from cultured SVF cells, and Oil Red “O” staining. We found that freezing CELT^PLUS fat with DMSO yields better results than without cryoprotection in all evaluated methods. Until non-toxic cryoprotective agents are tested on CELT^PLUS fat, we do not recommend initiating animal or human testing. Full article

Reactive oxygen species (ROS) act as double-edged swords in cancer biology—facilitating tumor growth, survival, and metastasis at moderate levels while inducing oxidative damage and cell death when exceeding cellular buffering capacity. To survive under chronic oxidative stress, cancer cells rely on robust antioxidant systems such as the glutathione (GSH) and thioredoxin (Trx), and superoxide dismutases (SODs). These systems maintain redox homeostasis and sustain ROS-sensitive signaling pathways including MAPK/ERK, PI3K/Akt/mTOR, NF-κB, STAT3, and HIF-1α. Targeting the antioxidant defense mechanisms of cancer cells has emerged as a promising therapeutic strategy. Inhibiting the glutathione system induces ferroptosis, a non-apoptotic form of cell death driven by lipid peroxidation, with compounds like withaferin A and altretamine showing strong preclinical activity. Disruption of the Trx system by agents such as PX-12 and dimethyl fumarate (DMF) impairs redox-sensitive survival signaling. Trx reductase inhibition by auranofin or mitomycin C further destabilizes redox balance, promoting mitochondrial dysfunction and apoptosis. SOD1 inhibitors, including ATN-224 and disulfiram, selectively enhance oxidative stress in tumor cells and are currently being tested in clinical trials. Mounting preclinical and clinical evidence supports redox modulation as a cancer-selective vulnerability. Pharmacologically tipping the redox balance beyond the threshold of cellular tolerance offers a rational and potentially powerful approach to eliminate malignant cells while sparing healthy tissue, highlighting novel strategies for targeted cancer therapy at the interface of redox biology and oncology. Full article

Neurologic complications remain a major cause of morbidity in patients undergoing surgical repair of acute type A aortic dissection (ATAAD). Near-infrared spectroscopy (NIRS) is used for continuous, noninvasive monitoring of cerebral oxygenation during cardiopulmonary bypass; however, its utility in predicting perioperative stroke remains inadequately defined. A retrospective cohort study was conducted in 175 patients who underwent ATAAD repair between 2015 and 2023. Patients were stratified by the occurrence of perioperative stroke (n = 47, 26.9%). Intraoperative NIRS data, including cerebral regional oxygen saturation (crSO₂) values at key procedural timepoints and signal variability with band power and crest factor, were analyzed in conjunction with demographic, anatomic, and postoperative variables. Patients with stroke exhibited significantly lower minimum NIRS values during deep hypothermic circulatory arrest (DHCA) (left: 46.7 (15.7–69.4) vs. 52.2 (22.0–81.6); right: 47.0 (23.3–78.5) vs. 56.3 (20.2–85.0); p = 0.03 and p < 0.01). Within the stroke group, NIRS signal variability was significantly greater (crest factor and standard deviation; p < 0.05) and showed blunted recovery post-DHCA. crSO₂ values below 50% were more frequent in the stroke group (p = 0.04). Right common carotid artery dissection was more prevalent in the stroke group (40% vs. 23%, p = 0.04). ICU length of stay was significantly increased in patients with stroke. Cerebral desaturation and NIRS signal instability during DHCA are significantly associated with perioperative stroke in ATAAD repair. These findings support the prognostic value of intraoperative cerebral oximetry in detecting critical ischemic thresholds and identifying at-risk perfusion patterns. Full article

Background/Objectives: Accurate prediction of pediatric appendicitis diagnosis, management, and severity is critical for clinical decision-making. We aimed to evaluate the predictive performance of a wide range of machine learning models, combined with various feature selection techniques, on a pediatric appendicitis dataset. A particular focus was placed on the role of ultrasound (US) image-descriptive features in model performance and explainability. Methods: We conducted a retrospective cohort study on a dataset of 781 pediatric patients aged 0–18 presenting to Children’s Hospital St. Hedwig in Regensburg, Germany, between January 2016 and February 2023. We developed and validated predictive models; machine learning algorithms included the random forest, logistic regression, stochastic gradient descent, and the light gradient boosting machine (LGBM). These were paired exhaustively with feature selection methods spanning filter-based (association and prediction), embedded (LGBM and linear), and a novel redundancy-aware step-up wrapper approach. We employed a machine learning benchmarking study design where AI models were trained to predict diagnosis, management, and severity outcomes, both with and without US image-descriptive features, and evaluated on held-out testing samples. Model performance was assessed using overall accuracy and area under the receiver operating characteristic curve (AUROC). A deep learner optimized for tabular data, GANDALF, was also evaluated in these applications. Results: US features significantly improved diagnostic accuracy, supporting their use in reducing model bias. However, they were not essential for maximizing accuracy in predicting management or severity. In summary, our best-performing models were, for diagnosis, the random forest with embedded LGBM feature selection (98.1% accuracy, AUROC: 0.993), for management, the random forest without feature selection (93.9% accuracy, AUROC: 0.980), and for severity, the LGBM with filter-based association feature selection (90.1% accuracy, AUROC: 0.931). Conclusions: Our results demonstrate that high-performing, interpretable machine learning models can predict key clinical outcomes in pediatric appendicitis. US image features improve diagnostic accuracy but are not critical for predicting management or severity. Full article

Background/Objectives: Cognitive impairment is one of the most common and debilitating clinical features of Multiple Sclerosis (MS). Neuropsychological assessment, however, is time-consuming and requires personal resources, so, due to limited resources in daily clinical practice, information on cognitive profiles is often lacking, despite its high prognostic relevance. Time-saving and effective tools are required to bridge this gap. This study evaluates the sensitivity and specificity of a revised version of TRACK-MS (TRACK-MS-R), a recently published screening tool to identify cognitive impairment in MS in a fast and reliable way, offering a balance between efficiency and diagnostic yield for the individual patient. Methods: In this prospective cross-sectional study, 102 MS patients and 94 age-, sex-, and education-matched healthy controls (HC) completed an extensive neuropsychological assessment, including TRACK-MS-R, to test for cognitive processing speed (Symbol Digit Modalities Test, SDMT) and verbal fluency (Regensburger Word Fluency Test, RWT). Sensitivity of TRACK-MS-R was assessed by using the BICAMS-M battery as a reference, and specificity was determined by comparing MS patients to HC. Results: TRACK-MS-R demonstrated high sensitivity (97.44%) when compared to the gold standard as represented by BICAMS-M for early and accurately detecting cognitive impairment in MS patients. Additionally, as a potential cognitive marker, TRACK-MS-R showed a specificity of 82.98% in distinguishing MS patients from healthy controls. Conclusions: TRACK-MS-R proves to be a highly sensitive and time-efficient screening tool for detecting cognitive impairment in patients with MS, while demonstrating good specificity compared to HC. Whereas high sensitivity is a prerequisite for a valid screening tool, its relatively modest specificity compared to BICAMS-M (62.9%) calls for caution in interpreting standalone results but instead indicates more extensive neuropsychological testing. Its briefness and diagnostic accuracy support its implementation in routine clinical practice, particularly in time-constrained settings. Full article

Background/Objectives: Lysophosphatidylcholine (LPC) is composed of various lipid species, some of which exert pro-inflammatory and others anti-inflammatory activities. However, most of the LPC species analyzed to date are reduced in the serum of patients with inflammatory bowel disease (IBD) compared to healthy controls. To our knowledge, the correlation between serum LPC species levels and measures of inflammation, as well as their potential as markers for monitoring IBD activity, has not yet been investigated. Methods: Thirteen LPC species, varying in acyl chain length and number of double bonds, were measured in the serum of 16 controls and the serum of 57 patients with IBD. Associations with C-reactive protein (CRP) and fecal calprotectin levels as markers of IBD severity were assessed. Results: Serum levels of LPC species did not differ between the healthy controls and the entire patient cohort. In patients with IBD, serum levels of LPC 16:1, 18:0, 18:3, 20:3, and 20:5, as well as total LPC concentrations, showed inverse correlations with both CRP and fecal calprotectin levels, indicating an association with inflammatory activity. Nine LPC species were significantly reduced in patients with high fecal calprotectin compared to those with low values. LPC species with 22 carbon atoms and 4 to 6 double bonds were not related to disease activity. Stool consistency and gastrointestinal symptoms did not influence serum LPC profiles. Corticosteroid treatment was associated with lower serum LPC 20:3 and 22:5 levels, while mesalazine, anti-TNF, and anti-IL-12/23 therapies had no significant impact on LPC concentrations. There was a strong positive correlation between LPC species containing 15 to 18 carbon atoms and serum cholesterol, triglycerides, and phosphatidylcholine levels. However, there was no correlation with markers of liver disease. Conclusions: Shorter-chain LPC species are reduced in patients with active IBD and reflect underlying hypolipidemia. While these lipid alterations provide insight into IBD-associated metabolic changes, they appear unsuitable as diagnostic or disease monitoring biomarkers. Full article

Mitochondria play a crucial role in adapting to fluctuating energy demands, particularly in various heart diseases. In addition to functional analyses such as the measurement of ROS or ATP, analysis of mitochondrial ultrastructure can be used to draw further conclusions about their functions and effects in tissue. In this protocol, we introduce a set of measurements to compare the ultrastructural and functional characteristics of human left ventricular mitochondria, using transmission electron microscopy (TEM). Measured parameters included mean size in µm², elongation, count, percental mitochondrial area in the measuring frame, and a conglomeration score. We also introduce a novel method of defining hydropic mitochondria as a comparable evaluation standard. With this cluster of measurement parameters, we aim to contribute a protocol for studying human mitochondrial morphology, distribution, and functionality. Full article

Introduction: Sex-specific differences in psychopharmacological treatment have gained increasing attention in adults, with studies showing that women often have higher serum concentrations of psychotropic drugs due to biological differences. However, despite recognition of these differences in adults, reference ranges for therapeutic drug monitoring (TDM) in general, but even more sex-specific therapeutic windows for psychotropic drugs, are lacking in children and adolescents, who may metabolize and respond to medications differently. Aim: The study aimed to investigate sex-specific differences in antidepressant (AD) and antipsychotic (AP) -treatment outcomes, and pharmacokinetics in childhood/adolescence. In particular, we examined differences in AD and AP serum levels and clinical effects, including adverse drug effects (ADEs) and therapeutic effectiveness. Methods: This study is part of the multicenter “TDM-VIGIL” pharmacovigilance project, which prospectively followed patients aged 6–18 years treated with AD and AP across 18 child psychiatric centers in German-speaking countries from 2014 to 2018. Clinical data, including drug concentrations (AD: fluoxetine, mirtazapine, (es)citalopram, sertraline; AP: aripiprazole, quetiapine, olanzapine, risperidone), were collected using an internet-based registry, and treatment outcomes and ADEs were assessed during routine visits. Statistical analyses were performed to examine sex differences in pharmacokinetics and clinical responses, adjusting for age, weight, and other confounders. Results: A total of 705 patients (66.5% girls, 24.7% <14 years, mean age of 14.6 years) were included. Female patients were slightly older, had lower body weight, and were more often diagnosed with depression and anorexia nervosa, while boys were more frequently diagnosed with hyperkinetic disorders and atypical autism. We found no sex differences in the serum concentrations of investigated drugs when adjusted for age and weight. In fluoxetine treatment in patients diagnosed with mood (affective) disorders, female sex was associated with the probability for very good therapy response (p = 0.04), as well as with moderate treatment response (p = 0.02) compared to no treatment response. Discussion: Our findings suggest that sex may not affect serum levels of investigated AD and AP in children/adolescents. However, treatment outcome of fluoxetine was associated with sex, with higher probability for a better outcome in female patients diagnosed with mood (affective) disorders. Full article

A triphenylphosphine-functionalized silica gel material, optimized for lead adsorption, was synthesized via a one-pot sol–gel reaction and characterized using FTIR and solid-state ¹³C and ²⁹Si NMR and XPS spectroscopy. The interaction between lead cations and phosphine groups was evaluated using the ³¹P NMR chemical shift tensor as a sensor. Two distinct types of phosphine groups, exhibiting different rotational mobility behaviors, were identified, with their ratio influenced by the presence of lead cations. These results suggest that the adsorption behavior of lead on this functionalized silica gel adsorbent can be directly evaluated by its lead–phosphorus interaction. This association was corroborated by the shifting of the binding energies of phosphorus functional groups after lead uptake in the XPS analysis. Full article

Objectives: Previous literature has already discussed the effects of age and sex on the diagnosis and treatment of malocclusion problems. However, this effect varies among different ethnic groups. These differences have not yet been investigated in many populations, such as Arab orthodontic patients and residents of Israel. Therefore, it is crucial to understand such variations in specific populations for better diagnosis and treatment. The main aim of this study is to provide novel knowledge concerning skeletal classes I and II among a cohort of Arab patients who are citizens of Israel. We used parameters obtained from lateral cephalograms to understand the variations among different sex and age subgroups. We also examined the correlations and performed principal component analysis (PCA). Methods: This study was based on the coded records of 394 Arab patients diagnosed with skeletal Class I occlusion (SCIO) or skeletal Class II malocclusion (SCIIMO), according to the individualized ANB (Calculated_ANB) of Panagiotidis and Witt. Results: Among patients with SCIO, males had a significantly more horizontal growth pattern (PFH/AFH) and anterior mandible rotation (ML-NSL) than females. Regarding patients with SCIIMO, female adults had more hyperdivergent jaw bases than adolescents (ML-NL) and a more posteriorly rotated mandible (ML-NSL). Spearman’s analysis revealed many significant correlations, like Calculated_ANB, ANB angle, and Wits appraisal. The PCA results showed a remarkable ability to explain 88.6% of the sample variance using four principal components. Conclusions: This research revealed new information regarding Arab orthodontic patients diagnosed with skeletal class I or II. The results demonstrate the differences between the two classes. In addition, this study demonstrated the variation and correlation of cephalometric parameters among different sex and age subgroups in skeletal class I and II Arab patients, especially considering Calculated_ANB. Therefore, this study highlights the need to consider these differences when diagnosing patients and to distinguish the differences across different sex and age subgroups in the diagnosis and treatment process. Furthermore, the PCA results showed the importance of ML-NSL, SN-Pg, PFH/AFH ratio, and NL-ML in explaining the data variance. Full article

The effective suppression of inflammation using disease-modifying therapies is essential in the treatment of multiple sclerosis (MS). Anti-CD20 monoclonal antibodies are commonly used long-term as maintenance therapies, largely due to the lack of reliable biomarkers to guide dosing and evaluate treatment response. However, prolonged use increases the risk of infections and other immune-mediated side effects. The unique ability of brain-derived blood extracellular vesicles (EVs) to cross the blood–brain barrier and reflect the central nervous system (CNS) immune status has sparked interest in their potential as biomarkers. This study aimed to assess whether blood-derived L1CAM⁺ EVs could serve as biomarkers of treatment response to rituximab (RTX) in patients with relapsing-remitting MS (RRMS). Serum samples (n = 25) from the baseline (month 0) and after 6 months were analyzed from the RTX arm of the ongoing randomized clinical trial OVERLORD-MS (comparing anti-CD20 therapies in RRMS patients) and were compared with serum samples from healthy controls (n = 15). Baseline cerebrospinal fluid (CSF) samples from the same study cohort were also included. EVs from both serum and CSF samples were characterized, considering morphology, size, and concentration, using transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). The immunophenotyping of EV surface receptors was performed using flow cytometry with the MACSPlex exosome kit, while label-free quantitative proteomics of EV protein cargo was conducted using a proximity extension assay (PEA). TEM confirmed the presence of EVs with the expected round morphology with a diameter of 50–150 nm. NTA showed significantly higher concentrations of L1CAM⁺ EVs (p < 0.0001) in serum total EVs and EBNA1⁺ EVs (p < 0.01) in serum L1CAM⁺ EVs at baseline (untreated) compared to in healthy controls. After six months of RTX therapy, there was a significant reduction in L1CAM⁺ EV concentration (p < 0.0001) and the downregulation of TNFRSF13B (p = 0.0004; FC = −0.49) in serum total EVs. Additionally, non-significant changes were observed in CD79B and CCL2 levels in serum L1CAM⁺ EVs at baseline compared to in controls and after six months of RTX therapy. In conclusion, L1CAM⁺ EVs in serum showed distinct immunological profiles before and after rituximab treatment, underscoring their potential as dynamic biomarkers for individualized anti-CD20 therapy in MS. Full article

Background/Objectives: Otolaryngologists are increasingly using head and neck ultrasound (HNUS). Determining whether a practitioner of HNUS has achieved adequate theoretical knowledge remains a challenge. This study assesses the performance of two large language models (LLMs) in generating multiple-choice questions (MCQs) for head and neck ultrasound, compared with MCQs generated by physicians. Methods: Physicians and LLMs (ChatGPT, GPT4o, and Google Gemini, Gemini Advanced) created a total of 90 MCQs that covered the topics of lymph nodes, thyroid, and salivary glands. Experts in HNUS additionally evaluated all physician-drafted MCQs using a Delphi-like process. The MCQs were assessed by an international panel of experts in HNUS, who were blinded to the source of the questions. Using a Likert scale, the evaluation was based on an overall assessment including six assessment criteria: clarity, relevance, suitability, quality of distractors, adequate rationale of the answer, and an assessment of the level of difficulty. Results: Four experts in the clinical field of HNUS assessed the 90 MCQs. No significant differences were observed between the two LLMs. Physician-drafted questions (n = 30) had significant differences with Google Gemini in terms of relevance, suitability, and adequate rationale of the answer, but only significant differences in terms of suitability compared with ChatGPT. Compared to MCQ items (n = 16) validated by medical experts, LLM-constructed MCQ items scored significantly lower across all criteria. The difficulty level of the MCQs was the same. Conclusions: Our study demonstrates that both LLMs could be used to generate MCQ items with a quality comparable to drafts from physicians. However, the quality of LLM-generated MCQ items was still significantly lower than MCQs validated by ultrasound experts. LLMs are therefore cost-effective to generate a quick draft for MCQ items that afterward should be validated by experts before being used for assessment purposes. In this way, the value of LLM is not the elimination of humans, but rather vastly superior time management. Full article

The aim of translucency-enhancing liquids (TEL) is to locally influence the phase composition of zirconia in order to increase its translucency. This study aimed to determine the influence of TEL on 3Y- and 4Y-TZP zirconia concerning roughness, hardness, wear, flexural strength, dynamic stability and fracture force of fixed dental prostheses after thermal cycling and mechanical loading. Two zirconia materials (4Y-TZP; 3Y-TZP-LA, n = 8 per material and test) were investigated with and without prior application of TEL. Two-body wear tests were performed in a pneumatic pin-on-block design (50 N, 120,000 cycles, 1.6 Hz) with steatite balls (r = 1.5 mm) as antagonists. Mean and maximum vertical loss as well as roughness (Ra, Rz) were measured with a 3D laser-scanning microscope (KJ 3D, Keyence, J). Antagonist wear was determined as percent area of the projected antagonist area. Martens hardness (HM; ISO 14577-1) and biaxial flexural strength (BFS; ISO 6872) were investigated. The flexural fatigue limit BFSdyn was determined under cyclic loading in a staircase approach with a piston-on-three-ball-test. Thermal cycling and mechanical loading (TCML: 2 × 3000 × 5 °C/55 °C, 2 min/cycle, H₂O dist., 1.2 × 10⁶ force á 50 N) was performed on four-unit fixed dental prostheses (FDPs) (n = 8 per group) and the fracture force after TCML was determined. Statistics: ANOVA, Bonferroni test, Kaplan–Meier survival, Pearson correlation; α = 0.05. TEL application significantly influences roughness, hardness, biaxial flexural strength, dynamic performance, as well as fracture force after TCML in 3Y-TZP. For 4Y-TZP, a distinct influence of TEL was only identified for BFS. The application of TEL on 3Y- or 4Y-TZP did not affect wear. TEL application has a strong effect on the mechanical properties of 3Y-TZP and minor effects on 4Y-TZP. All effects of the TEL application are of a magnitude that is unlikely to restrict clinical application. Full article

Additive manufacturing (AM), particularly laser powder bed fusion (L-PBF), provides unmatched design flexibility for creating intricate steel structures with minimal post-processing. However, adopting L-PBF for high-performance applications is difficult due to the challenge of predicting microstructure evolution. This is because the process is sensitive to many parameters and has a complex thermal history. Thin-walled geometries present an added challenge because their dimensions often approach the scale of individual grains. Thus, microstructure becomes a critical factor in the overall integrity of the component. This study focuses on applying cellular automata (CA) modeling to establish robust and efficient process–structure relationships in L-PBF of 316L stainless steel. The CA framework simulates solidification-driven grain evolution and texture development across various processing conditions. Model predictions are evaluated against experimental electron backscatter diffraction (EBSD) data, with additional quantitative comparisons based on texture and morphology metrics. The results demonstrate that CA simulations calibrated with relevant process parameters can effectively reproduce key microstructural features, including grain size distributions, aspect ratios, and texture components, observed in thin-walled L-PBF structures. This work highlights the strengths and limitations of CA-based modeling and supports its role in reliably designing and optimizing complex L-PBF components. Full article