Meta-analyses of observational and clinical studies conducted in recent years have raised serious doubts about the validity of the low-fat dietary recommendations introduced in the late 1970s/early 1980s, due to the absence of any convincing link between saturated fat and the risk of cardiovascular diseases. At the same time, long-term food supply statistics from the FAOSTAT database show that these recommendations were at the root of fundamental dietary changes in Western countries, which resulted in a lower consumption of eggs and red meat, a higher consumption of cereals and poultry, a decline in average protein quality and, overall, in a higher glycemic load of the diet. Because current views on human nutrition are based primarily on highly unreliable questionnaire data from observational studies, the purpose of this commentary is to provide an alternative ecological (country-level) perspective and to trace the consequences of these nutritional changes using the FAOSTAT database in combination with available anthropological and health statistics. This comparison shows a close connection between the decline in protein quality and the sudden reversal of the positive height trend in some Western countries, after ∼150 years of continuous growth, which points to suboptimal levels of child nutrition. The sharp increase in the prevalence of obesity and type 2 diabetes is strongly correlated with the increasing consumption of high-glycemic carbohydrates and sweeteners, and is also interconnected with the decrease in body height, because a high-quality, growth-stimulating diet during adolescence is inversely related to obesity. Given the long-term association between height and phenotypic IQ, the lower quality of nutrients in children's diet may also seriously affect intellectual potential and future civilizational development. In light of these findings, current nutritional strategies should be seriously reconsidered and recommended protein intakes for children must be urgently reevaluated.

• Keywords
• Child health, flynn effect, nutrition, obesity, physical growth,
• MeSH
• Diabetes Mellitus, Type 2 epidemiology   MeSH
• Diet * trends   MeSH
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Obesity * epidemiology   MeSH
• Body Height * MeSH
• Food Supply * statistics & numerical data   MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Person-centred care (PCC) is a fundamental principle in general practice, emphasising practices tailored to individual patient preferences, needs, and values. Despite the importance of PCC, general practitioners (GPs) face obstacles in effectively implementing it, with associated factors remaining unclear. OBJECTIVES: The PACE GP/FP study aims to explore GPs' attitudes towards PCC and the factors facilitating or hindering its implementation in daily practice across European countries. This paper outlines the PACE GP/FP study protocol. METHODS: The cross-sectional design with data collection via an online survey distribution to GPs in 24 European countries. Study instruments include two validated questionnaires (Perceived Stress Scale (PSS) and Patient Physician Orientation Scale (PPOS)) and additional items covering general information about the doctor and their practice, as well as facilitators and barriers to PCC. These additional items were specifically developed for the study, translated using the forward-backward method, evaluated through cognitive debriefing, and integrated into the REDCap platform to create language and country-specific survey links. The STROBE checklist guides the reporting of the manuscript. CONCLUSION: The PACE GP/FP study will provide a comprehensive exploration of GPs' attitudes towards PCC and the factors shaping its practice in Europe. The findings from the PACE GP/FP study will provide evidence for designing future implementation strategies and guide targeted interventions to promote PCC in primary care across Europe.

• Keywords
• Primary health care, general practice, person-centred care,
• MeSH
• Humans MeSH
• Patient-Centered Care * organization & administration   MeSH
• Attitude of Health Personnel * MeSH
• General Practice * MeSH
• General Practitioners * psychology   MeSH
• Cross-Sectional Studies MeSH
• Surveys and Questionnaires MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Europe MeSH

BACKGROUND: Plasma sulfur amino acids (SAAs), particularly cysteine, are associated with obesity. One proposed mechanism is the altered regulation of the stearoyl-CoA desaturase (SCD) enzyme. Changes in the SCD enzyme activity have been linked to obesity, as well as to plasma SAA concentrations. OBJECTIVE: This study aimed to investigate whether estimated SCD activity mediates the associations between plasma SAAs and measures of overall adiposity and specific fat depots. METHODS: We examined cross-sectional data from a subset of the Maastricht Study (n = 1129, 50.7% men, 56.7% with (pre)diabetes). Concentrations of methionine, total homocysteine, cystathionine, total cysteine (tCys), total glutathione (tGSH), and taurine were measured in fasting plasma. Outcomes included measures of overall, peripheral and central adiposity, and liver fat. SCD activity was estimated by ratios of serum fatty acids as SCD16 and SCD18 indices. The associations between plasma SAAs and measures of adiposity or liver fat were examined with multiple linear regression analysis. Multiple mediation analysis was used to investigate whether the significant associations were mediated by SCD16 and SCD18 indices. RESULTS: Plasma tCys was positively associated with all adiposity measures (β ranged from 0.15 to 0.30). SCD16 significantly mediated all associations (proportion mediated ranged from 5.1% to 9.7%). Inconsistent mediation effects were found for SCD18. Despite a significant inverse association of plasma tGSH with all adiposity measures (β ranged from -0.08 to -0.16), no significant mediation effect was found. CONCLUSIONS: Plasma tCys may promote excessive body fat accumulation via upregulation of SCD activity.

• Keywords
• Body fat depots, Obesity, Plasma sulfur amino acids, Stearoyl-CoA desaturase, Total cysteine,
• MeSH
• Adiposity * MeSH
• Cysteine * blood   MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Obesity blood   MeSH
• Cross-Sectional Studies MeSH
• Stearoyl-CoA Desaturase * metabolism   blood   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Cysteine * MeSH
• Stearoyl-CoA Desaturase * MeSH

The gradual phaseout of dental amalgam has contributed to a significant increase in the use of resin-based materials. While these materials offer several desirable properties, concerns persist regarding their biocompatibility, particularly the release of bisphenol A (BPA). BPA is an endocrine-disrupting chemical linked to adverse effects on human health, including reproductive, developmental, and metabolic disorders. Although food contact materials are the primary source of human BPA exposure and the contribution of dental materials is minor, the associated risks cannot be dismissed due to BPA's nonmonotonic dose-response relationship. In 2023, the European Food Safety Authority proposed a 20,000-fold reduction in the tolerable daily intake of BPA to 0.2 ng/kg body weight, citing immune system effects at extremely low doses. This proposal has sparked regulatory and scientific debate, as adopting such a stringent limit would effectively ban the use of BPA in food contact materials and many other products. Given this context, it is essential to assess the release of BPA from dental materials both in vitro and in vivo. However, data interpretation is complicated by methodological inconsistencies, including variations in material composition, specimen preparation, choice of extraction media, experimental duration, and analytical methods. In addition, pivotal differences in reporting results make it difficult to synthesize findings and draw reliable conclusions. This review examines the controversy surrounding BPA, critically evaluates evidence on its release from dental materials, and explores mitigation strategies. By highlighting gaps in knowledge and proposing future research directions, this review aims to provide clinicians, researchers, and policymakers with a clearer understanding of BPA-related complexities, ultimately contributing to patient safety and material innovation.

• Keywords
• biocompatibility, composite materials, endocrinology, resin(s), sealants, toxicology,
• MeSH
• Benzhydryl Compounds * adverse effects   analysis   MeSH
• Endocrine Disruptors * adverse effects   analysis   MeSH
• Phenols * adverse effects   analysis   MeSH
• Risk Assessment MeSH
• Humans MeSH
• Dental Materials * chemistry   adverse effects   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Benzhydryl Compounds * MeSH
• bisphenol A MeSH Browser
• Endocrine Disruptors * MeSH
• Phenols * MeSH
• Bisphenol A Compounds MeSH
• Dental Materials * MeSH

PURPOSE: The surgical treatment of endometriosis, which is routinely performed by minimally invasive approach, is developing towards an increasing complexity in deep endometriosis. While RAS appears to be gaining importance, there are few real-life data on its use for patients with endometriosis. The aim of this study is to investigate the current use of RAS in certified endometriosis centers in Central Europe. METHODS: In this international multicentric cross-sectional study, an online branching survey was sent to certified endometriosis centers in Austria, the Czech Republic, Germany, and Switzerland. This survey contained 47 questions including proportion of use, indications, advantages and barriers, technical aspects, and training in RAS. RESULTS: Of the 97 centers contacted, 66% (n = 64) participated. RAS is used for the treatment of endometriosis in 60.8% (n = 31) of the centers with access to a SR, which corresponds to 48.4% of all participating centers. In Austria, 81.8% (n = 9) of centers have SR access, respectively, 88.9% (n = 8) use RAS for endometriosis; in Switzerland, 91.6% (n = 11) and 36.4% (n = 4); and in Germany, 74.4% (n = 29) and 62.1% (n = 18). The reported advantages of RAS include precision (80%, n = 40), instrument mobility (74%, n = 37), and visualization (72%, n = 36). Compared to CLS, RAS is preferred in multidisciplinary cases (84.6%, n = 22), and overweight patients (61.5%, n = 16) and deep endometriosis (61.5%, n = 16). Specific anatomical indications for RAS vs. CLS include FU (57.7%, n = 15), C (53.9%, n = 14), and FB (50%, n = 13) (#Enzian classification). Patient outcomes of RAS compared to CLS are rated as advantageous in 69.2% (n = 18). The main barriers for RAS for centers without an SR include costs (100%, n = 12) and lack of scientific evidence (33.3%, n = 4). 69.2% (n = 18) have dedicated robotic teams, 42.3% (n = 11) have a second console, 69.2% (n = 18) have a simulator, and 34.6% (n = 9) have training programs. A total of 65.4% (n = 17) believes that RAS will replace CLS in selected cases, and 73.1% (n = 19) would prefer RAS if costs were equal. CONCLUSION: This study demonstrates that RAS is already being used in approximately half of the participating endometriosis centers. While the proportion of RAS procedures compared to CLS is increasing, it still remains comparatively low. Country-specific differences in the use of RAS are evident and are most likely linked to healthcare system structures. Participating centers report both technical and general surgical advantages, as well as specific benefits in cases of deep endometriosis. The main barriers include costs and a lack of scientific evidence. Further research is needed to evaluate the long-term role of RAS in the management of endometriosis.

• Keywords
• Deep endometriosis, Endometriosis, Endometriosis centers, Endometriosis surgery, MIGS, MIS, Minimally invasive surgery, RAL, RAS, Robot-assisted laparoscopy, Robot-assisted surgery, Robotic surgery, Robotic-assisted surgery,
• MeSH
• Endometriosis * surgery   MeSH
• Laparoscopy * methods   statistics & numerical data   MeSH
• Humans MeSH
• Cross-Sectional Studies MeSH
• Surveys and Questionnaires MeSH
• Robotic Surgical Procedures * statistics & numerical data   methods   education   MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Geographicals
• Czech Republic MeSH
• Germany MeSH
• Austria MeSH
• Switzerland MeSH

The study examines the link between economic growth and environmental sustainability in advanced economies from 1994 to 2023 within the LCC (Load Capacity Curve) hypothesis framework. Additionally, the study investigates the moderating role of ICT and environmental taxes in the linkage between economic growth and the Load Capacity Factor (LCF). Second-generation panel data analysis methods, namely CUP-FM and BA-OLS techniques, were employed for coefficient estimation, and the MMQR method was applied to reveal the differing effects of variables at quantile levels. Empirical findings indicate a U-shaped link between LCF and economic growth, thereby validating the LCC hypothesis for advanced economies in the long term. Additionally, direct positive effects of ICT and environmental taxes on LCF were observed, and it was determined that the interactions between GDP and ICT, as well as between GDP and environmental taxes, are positively related to LCF. According to the MMQR analysis, the negative effect of economic growth on LCF is weaker in the lower quantiles and stronger in the higher quantiles. The impact of ICT and environmental taxes on LCF is negative in the lower quantiles and turns positive in the higher quantiles. The interaction between economic growth and ICT was positive across all quantiles, with the highest effect occurring in the 90th quantile. Similarly, the interaction between environmental taxes and economic growth was positive across all quantiles, with the most substantial impact observed in the 10th and the weakest in the 90th quantile. While the control variables of renewable energy consumption positively impact LCF in all quantiles, the effect of financial development is adverse in the lower quantiles and positive in the higher quantiles. The findings underscore the importance of integrating growth, finance, digitalization, taxation, and energy policies to safeguard environmental capacity and promote sustainability in advanced economies.

• Keywords
• Economic growth, Environmental tax, ICT, Load capacity curve, Load capacity factor,
• Publication type
• Journal Article MeSH

BACKGROUND: Sleep apnea (SA), a prevalent sleep-related breathing disorder, disrupts normal respiratory patterns during sleep. This disruption can have a cascading effect on the body, potentially leading to complications in various organs, including the heart, brain, and lungs. Due to the potential for these complications, early and accurate detection of SA is critical. Electrocardiograms (ECG), due to their ability to continuously monitor heart rhythms and detect subtle changes in cardiac activity, such as heart rate variability and arrhythmias, which are often linked to sleep disruptions, have become crucial in identifying individuals at risk for SA. METHOD: In this study, we propose a hybrid neural network model named CNN-Transformer-LSTM that uses a single-lead ECG signal to detect SA automatically. This method captures spatial and temporal features in the ECG data to improve classification performance. Our model utilizes RR intervals (RRI) and R-peak signals derived from ECG data as input and then classifies SA and normal states on a per-segment and per-recording basis. We evaluated the model using the Physionet Apnea-ECG dataset, consisting of 70 single-lead ECG recordings annotated by medical professionals, and the UCD St. Vincent's University Hospital's sleep apnea database (UCDDB) containing polysomnogram records from 25 patients. RESULTS: Our model achieved an accuracy of 91.6% for per-segment classification on the Physionet Apnea-ECG dataset using hold-out validation and the highest accuracy of 94.1% using five-fold cross-validation. As for per-recording classification, our model achieved an accuracy of 100% and the highest correlation coefficient value of 0.9996 using five-fold cross-validation. On the UCDDB dataset, our model achieved an accuracy of 99.37% on the reduced dataset excluding 4 patients and 98.34% on the full dataset. Compared to previous works, our model improved the per-segment classification accuracy by nearly 3% over the existing best result, thereby demonstrating that our model outperforms existing state-of-the-art methods in accurately detecting SA from a single-lead ECG signal. CONCLUSION: These results highlight the effectiveness of the CNN-Transformer-LSTM model for SA detection and its potential to be used in SA detection devices for home health care and clinical settings.

• Keywords
• CNN-Transformer-LSTM, Deep learning, Detection, Electrocardiogram, Sleep apnea,
• MeSH
• Adult MeSH
• Electrocardiography * methods   MeSH
• Middle Aged MeSH
• Humans MeSH
• Neural Networks, Computer * MeSH
• Signal Processing, Computer-Assisted * MeSH
• Sleep Apnea Syndromes * diagnosis   physiopathology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Microtubules (MTs) undergo diverse posttranslational modifications that regulate their structural and functional properties. Among these, polyglutamylation-a dominant and conserved modification targeting unstructured tubulin C-terminal tails-plays a pivotal role in defining the tubulin code. Here, we describe a mechanism by which tubulin tyrosine ligase-like 11 (TTLL11) expands and diversifies the code. Cryo-electron microscopy revealed a unique bipartite MT recognition strategy wherein TTLL11 binding and catalytic domains engage adjacent MT protofilaments. Biochemical and cellular assays identified previously uncharacterized polyglutamylation patterns, showing that TTLL11 directly extends the primary polypeptide chains of α- and β-tubulin in vitro, challenging the prevailing paradigms emphasizing lateral branching. Moreover, cell-based and in vivo data suggest a cross-talk between polyglutamylation and the detyrosination/tyrosination cycle likely linked to the TTLL11-mediated elongation of the primary α-tubulin chain. These findings unveil an unrecognized layer of complexity within the tubulin code and offer mechanistic insights into the molecular basis of functional specialization of MT cytoskeleton.

• MeSH
• Cryoelectron Microscopy MeSH
• Humans MeSH
• Microtubules metabolism   MeSH
• Models, Molecular MeSH
• Peptide Synthases * metabolism   chemistry   genetics   MeSH
• Protein Processing, Post-Translational MeSH
• Tubulin * metabolism   chemistry   MeSH
• Protein Binding MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Peptide Synthases * MeSH
• tubulin polyglutamylase MeSH Browser
• Tubulin * MeSH

BACKGROUND AND OBJECTIVES: Focusing on pharmacokinetic-derived individual dose-intensity parameter values (DIPs), we modeled the pharmacokinetics of polyethylene glycol-conjugated asparaginase (PEG-ASNase) in all treatment phases and different trial groups of AIEOP-BFM ALL 2009. METHODS: Children with acute lymphoblastic leukemia received 1-10 weekly or biweekly repetitive doses (2500 U/m2/dose intravenously). A population pharmacokinetic (popPK) model was extended to all phases to describe the pharmacokinetics and the impact of anti-PEG- and anti-asparaginase-antibodies in the German/Czech group (2535 patients, aspartic acid β-hydroxamate (AHA) assay) and validated the model in the Italian group (1603 patients, medac asparaginase activity test (MAAT) assay). DIPs, also for 279 Australian patients, were derived. Allergic reactions and silent inactivation were exclusion criteria. RESULTS: Treatment phase dependency and drug accumulation were modeled by up to -60% lower clearance and -30% lower volume of distribution compared with the first administration in induction. Apart from the impact of high preexisting anti-PEG-antibody levels on clearance in induction, no further impact of antibodies was identified. Independent modelling of the Italian data (conversion factor 1.23/1.42: ≤ 600/> 600 U/L) confirmed the model. Time above 100 U/L correlated to the time-interval between the first and last dose within a phase, whereas the area under the concentration-time curve (AUC) was linked to the cumulative dose showing higher drug accumulation after repetitive doses than expected by linear extrapolation. CONCLUSION: A popPK model was adapted to all phases and different trial groups integrating asparaginase antibodies as long as they did not lead to silent inactivation or allergic reaction. The model allows strategic development of trial schedules and the calculation of intended or realized individual DIPs. TRIAL REGISTRATION: EU clinical trails register; European Union Drug Regulating Authorities Clinical Trials Database (EudraCT) Number 2007-004270-43.

• Publication type
• Journal Article MeSH

The SAR11-IIIb genus Fontibacterium within the order 'Ca. Pelagibacterales' is recognized for its ubiquitous presence in freshwater environments. However, cultivation limitations have hampered deeper ecophysiological understanding of this genus, with most data limited to lakes in the Northern Hemisphere. Here we present seven isolates representing two previously undescribed species, along with 93 high-quality metagenome-assembled genomes (MAGs) derived from a global survey across five continents. Phylogenomic analysis revealed 16 species forming nine distinct biogeographic clusters, indicating speciation patterns linked to water temperature and latitude. We observed endemic species restricted to African lakes, and quasi-endemic species confined to the Northern or Southern Hemisphere, which co-exist alongside cosmopolitan species. Metabolic profiling and growth experiments uncovered species- and strain-specific adaptations for nutrient uptake, along with unique pathways for sulfur metabolism. These findings provide a global-scale genomic and ecological overview for this underexplored lineage of freshwater SAR11.

• Publication type
• Journal Article MeSH