Search Results (2,759)

Reconstructing original cusp dimensions in worn molars represents a fundamental challenge across dentistry, anthropology, and paleontology, as dental wear obscures critical morphological information. In this proof-of-concept study, we present a standardized machine learning pipeline for predicting original cusp height, specifically the horn tips of the enamel–dentine junction (EDJ), in worn lower molars using three-dimensional morphometric data from micro-computed tomography (micro-CT). We analyzed 40 permanent lower first (M1) and second (M2) molars from four hominin groups, systematically evaluated across three wear stages: original, moderately worn (worn1), and severely worn (worn2). Morphometric variables including height, area, and volume were quantified for each cusp, with Random Forest and multiple linear regression models developed individually and combined through ensemble methods. To mimic realistic reconstruction scenarios while preserving a known ground truth, models were trained on unworn specimens (original EDJ morphology) and tested on other teeth after digitally simulated wear (worn1 and worn2). Predictive performance was evaluated using root mean square error (RMSE) and coefficient of determination (R²). Our results demonstrate that under moderate wear (worn1), the ensemble models achieved normalized RMSE values between 11% and 17%. Absolute errors typically below 0.25 mm for most cusps, with R² values up to ~0.69. Performance deteriorated under severe wear (worn2), particularly for morphologically variable cusps such as the hypoconid and entoconid, but generally remained within sub-millimetric error ranges for several structures. Random Forests and linear models showed complementary strengths, and the ensemble generally offered the most stable performance across cusps and wear states. To enhance transparency and accessibility, we provide a comprehensive, user-friendly software pipeline including pre-trained models, automated prediction scripts, standardized data templates, and detailed documentation. This implementation allows researchers without advanced machine learning expertise to explore EDJ-based reconstruction from standard morphometric measurements in new datasets, while explicitly acknowledging the limitations imposed by our modest and taxonomically unbalanced sample. More broadly, the framework represents an initial step toward predicting complete crown morphology, including enamel thickness, in worn or damaged teeth. As such, it offers a validated methodological foundation for future developments in cusp and crown reconstruction in both clinical and evolutionary dental research. Full article

Phospholipids are essential membrane constituents that regulate diverse cellular processes, yet most current workflows rely on relative quantification using high-resolution LC–MS. We developed and validated a highly selective targeted method that couples liquid chromatography with differential mobility spectrometry and tandem mass spectrometry (LC–DMS–MS/MS), providing enhanced selectivity and reduced background noise. The assay quantifies 63 phospholipid species across four classes, achieving excellent recoveries and limits of quantification in the low ng per mg tissue range. Applied to tissues from a colon cancer study in mice, the method enabled the absolute quantification of 47 species, 22 of which were significantly increased in tumor tissue versus adjacent non-tumor tissue. While phosphatidylcholines were the most abundant class overall, the largest fold changes were observed in long-chain phosphatidylglycerol and phosphatidylethanolamine species. LC–DMS–MS/MS thus offers a robust, selective platform for absolute phospholipid quantification and for detecting disease-associated lipid remodeling. Full article

The administration of various medications can induce bone loss as an adverse effect and may result in drug-induced osteoporosis, an important and clinically relevant form of secondary osteoporosis associated with an increased fracture risk. This review summarizes the skeletal effects of selected commonly used drugs with respect to bone metabolism, bone mineral density, and fracture outcomes. Medications may exert direct effects on osteoblasts and/or osteoclasts, leading to impaired bone remodeling and reduced bone mass. Alternatively, indirect mechanisms may contribute to skeletal damage, including disturbances in calcium and vitamin D metabolism with subsequent secondary hyperparathyroidism, as well as therapy-induced hypogonadism. Drug classes frequently associated with drug-induced osteoporosis during long-term use include glucocorticoids, aromatase inhibitors, androgen-deprivation therapy, thyroxine, proton pump inhibitors, anticoagulants (heparin and vitamin K antagonists), antidepressants, neuroleptics, and thiazolidinediones. Importantly, this overview represents a selection of relevant agents and does not aim to provide an exhaustive list. When prescribing potentially bone-damaging medications over extended periods, particularly in older individuals, bone health should be proactively considered. Evaluation should include laboratory assessment, fracture risk estimation (e.g., FRAX^®), and bone mineral density measurement when appropriate. Adequate calcium and vitamin D intake should be ensured, and guideline-based osteoporosis therapy initiated when indicated. Full article

Objectives: The Impostor Phenomenon (IP), defined as persistent self-doubt despite objective success, has been extensively researched in adults. In contrast, empirical research on children and adolescents remains limited. Methods: The present study examines the prevalence, correlates, and potential risk as well as protective factors of the IP in a sample of 286 participants (56.6% female, 42.7% male, and 0.7% diverse) aged 8–18 years (M = 11.75, SD = 2.50). Participants were recruited from four distinct German subsamples between 2022 and 2024, including a clinically vulnerable group. The study employed a cross-sectional survey design administered to children and adolescents. Results: The results of the study indicate the presence of the IP as early as primary school age, with increasing intensity during adolescence. The study identified robust correlations between the IP and neuroticism, extraversion, conscientiousness, and self-esteem. In the present study, children and adolescents exhibiting depressive–anxious symptomatology demonstrated significantly elevated impostor scores in comparison to those manifesting other disorders. Furthermore, the study yielded negative associations between impostorism and various personal resources (e.g., optimism, self-efficacy) and family resources (e.g., parental support, authoritative parenting style). Conclusions: The present findings underline the importance of early intervention in addressing impostor feelings among younger age groups. In conclusion, the present findings contribute to our understanding of the IP etiology and underscore the importance of understanding the IP during formative years to inform prevention and intervention strategies. Full article

Endometriosis (EM) is a chronic inflammatory disease characterized by the growth of endometrial-like tissue outside the uterus, yet its molecular mechanisms remain poorly understood. This study investigated the expression of mucins (MUC1, MUC2, MUC5AC, MUC6, MUC16) and their O-glycans in endometriotic lesions, given their roles in epithelial protection, adhesion, and immune modulation. Using immunohistochemistry, Western blotting, lectin profiling, histochemical staining, and transcriptomic analysis, we compared mucin levels and glycosylation patterns in eutopic and ectopic tissues from women with and without endometriosis and measured mucin-derived tumor markers in serum (CA 125/MUC16 and CA 15-3/MUC1) and peritoneal fluid (CA 125/MUC16). The results showed significant upregulation of all mucins in EM biopsies, with increased MUC1 transcript levels, while MUC6 and MUC16 protein levels did not always align with transcripts. Yet, tumor markers CA 125 and CA 15-3 showed no significant differences between groups. Looking at mucin distribution in biopsies of peritoneal (pEM), deep infiltrating and ovarian EM, MUC1 was significantly overexpressed in lesions of all EM forms, while MUC5AC was significantly elevated in pEM. Lectin analysis revealed specific glycan changes, including elevated core-1 O-glycans and α(1-2)-linked fucosylation, while sialylation remained unchanged. These findings demonstrate consistent mucin dysregulation and glycan alterations, implicating their roles in epithelial adhesion, immune evasion, and lesion persistence. Mucin biology thus emerges as a promising target for diagnostic and therapeutic strategies in endometriosis. Full article

Objectives: The study aims to assess the strategies used to estimate antimicrobial consumption (AMC) and the barriers encountered in data collection. It also addresses the perception about AMC based on the World Health Organization (WHO) definition. Methodology: The qualitative study adhered to the standard consolidated criteria for reporting qualitative studies (COREQ) guidelines. It involved stakeholders from diverse sectors, i.e., regulatory bodies, the pharmaceutical industry, international health organizations, policy experts, medical professionals, veterinary doctors, and academia (nursing, medicine, and pharmacy). A total of 37 in-depth interviews were conducted using a semi-structured interview schema. The interviews were recorded and transcribed verbatim. Codes were generated afterward and organized into themes. Results: Data analysis yielded five themes consisting of (i) Perception about Antimicrobial Consumption, AWaRe (Access, Watch, Reserve) classification and related terms, (ii) Antimicrobial Consumption: Policy Design, (iii) Data management and record keeping for the Estimation of Antimicrobial Consumption, (iv) Levels of Estimation for Antimicrobial consumption and Organizations, and (v) Challenges and suggested solutions in estimation of AMC: One health approach is the way forward. Conclusions: The study concluded that AMC and AMR are two sides of the same coin. The solution to AMR and excessive AMC is to re-evaluate the policy and implement legislation strictly. Efforts focused on irrational prescribing and unsupervised OTC sales of antimicrobials. This will help in reducing the consumption of broad-spectrum antimicrobials. Full article

Maca (Lepidium meyenii Walp.), a Brassicaceae species native to the high Andes of Peru, has gained global attention as a functional food and herbal medicinal product due to its endocrine-modulating, fertility-enhancing, and neuroprotective properties. Although numerous studies have addressed its biological effects, a systematic and up-to-date summary of its chemical constituents and analytical methodologies is lacking. This review aims to provide a critical overview of the chemical constituents of L. meyenii and to evaluate analytical studies published between 2000 and 2025, focusing on recent advances in extraction strategies and qualitative and quantitative analytical techniques for quality control. Major compound classes include macamides, macaenes, glucosinolates, and alkaloids, each contributing to maca’s multifaceted activity. Ultra-(high-)performance liquid chromatography (U(H)PLC), often coupled with ultraviolet, diode array, or mass spectrometric detection, is the primary and most robust analytical platform due to its sensitivity, selectivity, and throughput, while ultrasound-assisted extraction improves efficiency and reproducibility. Emerging techniques such as metabolomics and chemometric approaches enhance quality control by enabling holistic, multivariate assessment of complex systems and early detection of variations not captured by traditional univariate methods. As such, they provide complementary, predictive, and more representative insights into maca’s phytochemical complexity. The novelty of this review lies in its integration of conventional targeted analysis with emerging approaches, comprehensive comparison of analytical workflows, and critical discussion of variability related to phenotype, geographic origin, and post-harvest processing. By emphasizing analytical standardization and quality assessment rather than biological activity alone, this review provides a framework for quality control, authentication, and safety evaluation of L. meyenii as a functional food and dietary supplement. Full article

Background: Semi-occluded vocal tract exercises (SOVTE) improve vocal quality and capacity. Water resistance therapy (WRT), a specific form of SOVTE with a tube submerged under water, generates increased and oscillating oral pressure through bubble formation during phonation, thereby influencing transglottal pressure and vocal fold dynamics. While the physiological effects of WRT using tube-based systems have been extensively studied, the influence of vowel-specific vocal tract configurations during WRT remains unclarified. This study examined how different vowel qualities during WRT affect vocal fold oscillation using the DoctorVox^® mask, which allows near-natural mouth opening and vowel articulation. Methods: Ten vocally healthy, untrained adults (25–50 years) performed a continuous vowel glide (/i/–/a/–/u/-/i/) at constant fundamental frequency and habitual loudness during WRT using the DoctorVox^® mask, with the tube submerged 2 cm in water. Simultaneous recordings included transnasal high-speed videoendoscopy (20,000 fps), electroglottography (EGG), acoustic signals and intra-tube oral pressure measurements. Glottal area waveforms (GAW) were derived to calculate the open quotient (OQ_GAW) and closing quotient (ClQ_GAW). Analyses were conducted separately for intra-tube pressure maxima, minima and intermediate phases within the bubble cycle during WRT. Statistical analysis used Wilcoxon signed-rank tests with Bonferroni correction. Results: In the baseline condition without WRT, significant vowel-related differences were found: /u/ showed a higher open quotient than /i/ and /a/ (p < 0.05) and a higher closing quotient than /a/ (p < 0.05). During WRT, these vowel-specific differences were no longer statistically significant. A non-significant trend toward reduced OQ_GAW during WRT was observed, most notably for /u/, while differences between pressure phases within the bubble cycle were minimal. Conclusions: WRT using the DoctorVox^® mask reduces vowel-specific differences in vocal fold vibration patterns, suggesting that for voice therapy, vowel quality modifications during WRT have little impact on vocal outcomes. Full article

Peptide arrays represent a powerful tool for investigating a wide application field for biomedical questions. This review summarizes recent applications of peptide chips in oncology, with a focus on tumor microenvironment, metastasis, and drug mechanism of action for various cancer types. These high-throughput platforms enable the simultaneous screening of thousands of peptides. We report on recent achievements in peptide array technology for tumor microenvironments, an enhanced ability to decipher complex cancer-related signaling pathways, and characterization of cell-adhesion-mediating peptides. Furthermore, we highlight the applications in high-throughput drug screenings for development of immune therapies, e.g., the development of novel neoantigen therapies of glioblastoma. Moreover, epigenetic profiling using peptide arrays has uncovered new therapeutic targets across various cancer types with clinical impact. In conclusion, we discuss artificial intelligence-driven peptide array analysis as a tool to determine tumor origin and metastatic state, potentially transforming diagnostic approaches. These innovations promise to accelerate the development of precision cancer approaches. Full article

Background/Objectives: Bioresorbable polylactic acid (PLA) matrices have shown promise in supporting wound healing through their biocompatibility, tissue integration, and potential involvement in immune regulatory mechanisms. This study aimed to analyze the clinical performance of a PLA-based matrix in the treatment of chronic wounds under real-world conditions in a single-center setting. Methods: This retrospective study included patients with chronic wounds treated with the polylactic acid matrix at Evangelisches Waldkrankenhaus Spandau between February 2023 and February 2025. Wounds were surgically debrided in the operating room prior to matrix application. The matrix remained in place until resorption or detachment, with reapplications occurring at a mean interval of approximately 14 days. Data was anonymized and analyzed descriptively. Results: A total of 14 patients with 16 chronic wounds were treated in this study. The mean patient age was 76.1 years. The most common underlying causes were ischemia and trauma, with an average wound size of 23.6 cm². Complete wound closure was achieved in 15 out of 16 cases (93.8%), with a mean time to complete wound closure of 72.9 days. The average duration of hospitalization was 24.8 days. Conclusions: The polylactic acid matrix demonstrated a high rate of short-term wound closure in a heterogeneous cohort of chronic wounds, with a mean time to closure of 73 days and no requirement for skin grafting. Further prospective studies with standardized long-term follow-up are warranted. Full article

Bacteriophages, viruses that target bacteria, offer a promising alternative to antibiotics in the face of escalating bacterial resistance. Despite their discovery over a century ago, their widespread adoption has been impeded by regulatory challenges, limited funding, and the dominance of antibiotics. This review evaluates the current status of phage therapy by examining a comprehensive literature search, applying predefined inclusion and exclusion criteria. The review assesses selected scientific reports and clinical studies for their safety and efficacy profiles. Our findings indicate that advancements in phage therapy involve critical steps such as rapid bacterial detection, effective isolation, production, purification of phage preparations, and understanding their interactions with the host. Clinical studies generally show promising safety profiles with fewer adverse events compared to controls, and some trials suggest efficacy even at lower phage titers. Case reports further highlight phage therapy’s potential, demonstrating high success rates and minimal adverse events, although caution is advised due to potential biases. Despite promising results, significant research gaps remain, primarily due to the limited number of large-scale, well-designed clinical trials. Full article

Iridium pyridine diimine (PDI) complexes provide a versatile platform for highly reactive Ir–nitrido species with pronounced multiple-bond character, capable of activating H–H, C–H, Si–H, and even C–C bonds. Building on this chemistry, we extended our studies to a system with a terminal Ir–S bond, starting from our recently reported PDI–Ir–SH complex, which exhibits partial multiple-bond character. Upon addition of the 2,4,6-tri-tert-butylphenoxy radical, the corresponding phenol and a tentative Ir–S• radical intermediate are formed at ambient temperature. DFT and LNO-CCSD(T) calculations consistently reveal a low barrier for this process, with the spin density localized primarily on sulfur, accounting for subsequent S–S coupling reactions. Instead of the anticipated dimeric disulfido Ir–S₂–Ir complex formed along a least-motion pathway, a trisulfido Ir–S₃–Ir species was obtained, and characterized by NMR spectroscopy, X-ray crystallography and mass spectrometry. The formation mechanism of the trisulfido complex was further elucidated by DFT calculations. Remarkably, the sulfur-bridge formation is thermally reversible, regenerating the monomeric sulfanido Ir–SH complex. The origin of the hydrogen atom was investigated using H₂, D₂, and deuterated solvents. Full article

Under the dual pressures of rapid urbanization and climate change, urban expansion in high-density estuarine urban agglomerations has intensified economic–ecological trade-offs in the aquatic–terrestrial ecotone, necessitating land-use planning that reconciles economic growth with ecological protection. Here, we integrated linear programming with the CLUE-S model and incorporated marine–terrestrial integration objectives and typical natural disturbance factors. With this approach, a landscape pattern simulation framework capable of jointly optimizing ecological and economic benefits was developed. The framework was applied to the estuarine aquatic–terrestrial ecotone of the Pearl River Delta. This study drew on a land-use dataset, landscape dynamics, socioeconomic and biophysical drivers, and regional planning constraints to conduct simulation experiments under alternative development scenarios. The model achieved a Kappa coefficient of 0.904. From 2010 to 2020, built-up land expanded rapidly and encroached on ecological space. Simulations indicated that the natural evolution scenario increased fragmentation and ecological conflicts despite economic gains, whereas the sustainable development scenario balanced expansion and protection, reduced forestland fragmentation, safeguarded key ecological spaces, and improved ecological benefits while maintaining economic growth. Ecological benefits in the coastal aquatic–terrestrial ecotone from −0.2 to 0 km increased by 283.3%. The framework embeds land-use dynamics and spatial constraints, providing decision support for territorial spatial planning and ecological security pattern optimization. Full article

Pain in endometriosis involves not only nociceptive but also neuropathic and neurogenic components, reflecting its complex nature. Histamine, a biogenic amine, has emerged as a critical mediator connecting inflammation and nerve sensitization. This study aimed to characterize histamine receptor (HRH1–HRH4) expression, localization, and related inflammatory mediators in peritoneal, deep infiltrating, and ovarian endometriosis. Gene expression datasets were analyzed, and immunofluorescence staining of endometriotic lesions was performed using immune and neuronal markers. Histamine and its metabolite methylhistamine were quantified in serum, peritoneal fluid, and urine samples. HDC expression was significantly elevated in all endometriotic lesions compared with controls (all p < 0.01), paralleling increased IL-6, COX-2, NGF, and NGFR levels (p < 0.0001). In contrast, HRH1–HRH4 transcript levels showed no significant differences between groups. Immunofluorescence demonstrated robust HRH1–HRH4 protein expression in epithelial, immune, and nerve fibers, with subtype-specific colocalization patterns. Serum histamine concentrations were significantly higher in endometriosis patients than controls (0.484 vs. 0.153 ng/mg protein; p = 0.0014), whereas peritoneal histamine and urinary methylhistamine showed no group differences. Overall, these findings highlight histamine signaling as a potentially important component of endometriosis pathophysiology and point toward new directions for mechanistic studies and therapeutic exploration. Full article

Neonatal hyperoxia induces oxidative and inflammatory stress that disrupts cardiac maturation and contributes to long-term cardiovascular morbidity in individuals born preterm. Cannabidiol (CBD), a non-psychoactive phytocannabinoid with antioxidant and anti-inflammatory properties, has demonstrated protective effects in neonatal hyperoxic injury in other organs; however, its impact on the developing heart remains unclear. This study investigated whether CBD mitigates hyperoxia-induced cardiac injury in a neonatal mouse model. Newborn mice were exposed to 80% O₂ for 48 h from postnatal day (P)5 to P7 and received vehicle, 10 mg/kg CBD, or 30 mg/kg CBD intraperitoneally, while controls remained in room air. Hearts were collected at P7 or after recovery until P14. Hyperoxia triggered oxidative stress (Nrf2), inflammation (IL1β, TNFα, IL6, CXCL1; p < 0.05), and dysregulated apoptosis/autophagy, leading to reduced cardiomyocyte proliferation (Ki67⁺ −50% at P14; p < 0.01) and adverse remodeling (hypertrophy, fibrosis; p < 0.01). CBD attenuated these responses and normalized autophagy (Atg5, Atg12; p < 0.05). Notably, 10 mg/kg CBD, but not 30 mg/kg, preserved proliferative capacity and reduced wall thickness, suggesting a narrow therapeutic window, while both doses limited collagen deposition and apoptosis (Casp3, AIF; p < 0.05). Several effects were sex-dependent, with males exhibiting more pronounced long-term structural and proliferative impairments and greater responsiveness to low-dose CBD. These findings identify CBD as a potential cardioprotective modulator of neonatal hyperoxia-induced injury and highlight the importance of dose- and sex-specific mechanisms in early cardiac maturation. Full article