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

Induced pluripotent stem cell (iPSC) derived hippocampal dentate granule cell-like neurons from individuals with bipolar disorder (BD) are hyperexcitable and more spontaneously active relative to healthy control (HC) neurons. Furthermore, these abnormalities are normalised after the application of lithium in neurons derived from clinical lithium responders (LR) only. How these abnormalities impact hippocampal microcircuit computation is not understood. We aimed to investigate the impacts of BD-associated abnormal granule cell (GC) activity on pattern separation (PS) using a computational model of the dentate gyrus. We used parameter optimization to fit the parameters of biophysically realistic granule cell (GC) models to electrophysiological data from iPSC GCs from patients with BD. These cellular models were incorporated into dentate gyrus networks to assess impacts on PS using an adapted spatiotemporal task. Relationships between BD, lithium and spontaneous activity were analysed using a linear mixed-effects model. Lithium and BD negatively impacted PS, consistent with clinical reports of cognitive slowing and memory impairment during lithium therapy. By normalising spontaneous activity levels, lithium improved PS performance in LRs only. Improvements in PS after lithium therapy in LRs may therefore be attributable to the normalisation of spontaneous activity levels, rather than reductions in GC intrinsic excitability as we hypothesised. Our results mirror previous research demonstrating that mnemonic discrimination improves after lithium therapy in lithium responders only, supporting a hypothesised link between behavioural mnemonic discrimination and dentate gyrus PS. Our work can be expanded to also consider the effects of lithium-induced neurogenesis on PS.

• MeSH
• Antimanic Agents * pharmacology   MeSH
• Bipolar Disorder * drug therapy   physiopathology   MeSH
• Adult MeSH
• Dentate Gyrus * physiopathology   drug effects   MeSH
• Induced Pluripotent Stem Cells drug effects   MeSH
• Humans MeSH
• Lithium * pharmacology   MeSH
• Models, Neurological * MeSH
• Neurons * drug effects   physiology   MeSH
• Computer Simulation MeSH
• Lithium Compounds * pharmacology   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Antimanic Agents * MeSH
• Lithium * MeSH
• Lithium Compounds * MeSH

BACKGROUND: Urban environments exert strong pressures on animal behavior, leading to altered fear responses to humans. Species with a longer history of urban presence and greater tolerance to urban environments are expected to show reduced fear responses towards humans. Here, we examined whether avian flight initiation distance (a proxy of fear)-the distance at which a bird flees from an approaching human-is associated with a species' timing of urban colonization (i.e., when it has started to breed in urban areas) and with present-day urban tolerance (i.e., how common it is in the city). Unlike previous studies which paired avian fear responses and urbanization timing from different regions, we collected both in the same city (Prague, Czechia), minimizing regional differences in urban history and providing a more rigorous test of the link between urbanization timing and avian fear responses. RESULTS: Using standardized data from 4420 flight initiation distance observations across 68 species, we applied Bayesian phylogenetic mixed models while controlling for ecological and contextual variables. We found that species with a longer urban history (i.e., earlier timing of urban colonization) showed significantly shorter flight initiation distances, suggesting reduced fear responses. In contrast, present-day urban tolerance based on breeding commonness was not related to flight initiation distance variation. CONCLUSIONS: We found that the timing of urban colonization better predicts reduced fear of humans in birds than present-day urban tolerance, emphasizing the role of long-term behavioral filtering and/or selection in shaping urban wildlife behavior. By explicitly separating urbanization time from contemporary urban commonness within a single city and analyzing individual-level fear responses, our study shows that earlier urban colonizers exhibit consistently shorter escape distances, reflecting cumulative long-term processes rather than short-term plasticity alone. These findings highlight the importance of incorporating urban colonization history into behavioral ecology and urban wildlife management frameworks.

• Keywords
• Birds, Flight initiation distance, Monitoring, Urban habitats, Urban tolerance, Urbanization time,
• MeSH
• Bayes Theorem MeSH
• Time Factors MeSH
• Flight, Animal MeSH
• Humans MeSH
• Birds * physiology   MeSH
• Fear * MeSH
• Urbanization * MeSH
• Cities MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH
• Cities MeSH

BACKGROUND: The primary signals of sex determination in insects are diverse and evolve erratically. This also appears to be the case with moths and butterflies. In the silkworm Bombyx mori, female development is triggered by a W chromosome-derived Feminizer (Fem) piRNA that degrades the mRNA of the Z-linked Masculinizer (Masc) gene, which controls male development. We investigated whether this mechanism is conserved in another group of Lepidoptera. RESULTS: We identified a putative feminizing piRNA and many partial copies of the EkMasc gene on the W chromosome of Ephestia kuehniella. The piRNA is generated by a repetitive W-linked sequence named E. kuehniella Moth-overruler-of-masculinization (EkMom). EkMom piRNA shows high similarity to a region of Z-linked EkMasc and is expressed at the onset of female development, but has no relationship to the B. mori Fem piRNA. We then mapped small RNA-seq data from embryos of the related Plodia interpunctella to the PiMasc gene and identified a single small RNA, a PiMom piRNA, able to target PiMasc and with high sequence identity to the EkMom piRNA. Both the PiMom and EkMom repeats are present in high copy number and form a single cluster on the W chromosome. In both species, the Mom piRNA is responsible for Masc mRNA cleavage, clearly demonstrating that the Mom piRNA triggers female development. CONCLUSIONS: Our study provides multiple lines of evidence that Mom piRNA is the primary sex-determining signal in two pyralid moths and highlights a possible pathway for the origin of feminizing piRNAs in Lepidoptera. The similarity in female sex determination between the phylogenetically distant species suggests convergent evolution of feminizing piRNAs in Lepidoptera.

• Keywords
• Ephestia kuehniella, Masculinizer, Plodia interpunctella, Feminizing piRNA, Lepidoptera, Sex chromosomes, Sex determination, Small RNA-seq,
• MeSH
• Biological Evolution * MeSH
• RNA, Small Interfering * genetics   MeSH
• Evolution, Molecular * MeSH
• Moths * genetics   MeSH
• Piwi-Interacting RNA MeSH
• Sex Chromosomes * genetics   MeSH
• Sex Determination Processes * genetics   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• RNA, Small Interfering * MeSH
• Piwi-Interacting RNA MeSH

Head and neck squamous cell carcinoma (HNSCC), the seventh most common cancer worldwide, has become more closely linked to poor lifestyle habits. Despite improvements in cancer treatment approaches, patients with stage I-II HNSCC have a 70-90% 5-year survival rate, and for patients with advanced stages III-IV, this rate falls to about 40%. This controversy is all about the heterogeneity of HNSCC. Finding diagnosis and prognosis biomarkers has the potential to make significant improvements in the life expectancy and overall health of these patients. The combination of bioinformatics and machine learning has facilitated the finding of the best markers for HNSCC. In this regard, RNA expression data were obtained to identify genes that were expressed differently (DEGs) and utilize a deep learning algorithm to identify genes that exhibited significant variability. In addition, correlations between clinical data and DEGs, the building of a Receiver Operating Characteristic (ROC) curve, and the prediction of tumor-infiltrating immune cells were analyzed. Deep learning analysis identified diagnostic and prognostic biomarkers strongly associated with carcinogenesis, such as KRT33B, KRTAP3-3, C14orf34, and ACADM. In addition, after analyzing the ROC curve, it was found that the combination of ACADM, KRT33B, and C14orf34 is the most practical combination of diagnostic markers. This combination achieved sensitivity, specificity, and Area Under the Curve (AUC) values of 0.92, 0.86, and 0.93, respectively.

• Keywords
• Bioinformatics, Gene, Head and neck squamous cell carcinoma, Machine learning,
• Publication type
• Journal Article MeSH

OBJECTIVES: To explore the prevalence and distribution of ultrasound-detected lesions indicating structural damage at the enthesis (e.g., bone erosions, enthesophytes, and calcifications) in patients with spondyloarthritis (SpA), comparing those with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA), and to investigate the demographic, clinical, and metabolic factors linked to these lesions. METHODS: A cross-sectional analysis was conducted using data from the DEUS study, a multicentre investigation involving 20 rheumatology centres and including 413 patients with SpA (224 with axSpA and 189 with PsA). All participants underwent standardized clinical and ultrasound assessment of the large lower limb entheses (quadriceps tendon, proximal and distal patellar tendons, Achilles tendon, and plantar fascia). Entheseal structural lesions were explored by ultrasound and classified according to OMERACT definitions. Bivariate analyses and multivariate logistic regression were used to assess associations between ultrasound lesions and SpA patients' characteristics. RESULTS: In SpA patients, enthesophytes were the most common lesion (78.7 %), followed by calcifications (43.6 %) and bone erosions (24.9 %). Enthesophytes were more prevalent in PsA (86.8 %) compared to axSpA (71.9 %) (p < 0.001), with no significant differences in erosions and calcifications. However, lesion distribution varied across different entheses. Multivariate analysis revealed that entheseal erosions were significantly associated with inflammatory markers, HLA-B27 positivity, clinical enthesitis, and longer disease duration. Enthesophytes were significantly linked to PsA, psoriasis, clinical enthesitis, and longer disease duration. Calcifications were positively associated with hypertension, metabolic syndrome, and obesity. All lesions were associated with biologic DMARD use. CONCLUSIONS: This study reveals a high prevalence of ultrasound-detected structural damage at the enthesis and identifies distinct SpA phenotypes based on these findings.

• Keywords
• Calcifications, Enthesitis, Enthesophytes, Erosions, OMERACT, Structural damage, Ultrasound,
• MeSH
• Achilles Tendon diagnostic imaging   MeSH
• Adult MeSH
• Enthesopathy * diagnostic imaging   MeSH
• Phenotype MeSH
• Middle Aged MeSH
• Humans MeSH
• Cross-Sectional Studies MeSH
• Arthritis, Psoriatic * diagnostic imaging   MeSH
• Spondylarthritis * diagnostic imaging   MeSH
• Ultrasonography MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

Inhalation of radon and its short-lived progeny is one of the most significant contributors to the total effective dose from natural sources of ionising radiation. Exposure to radon progeny represents a substantial health risk, primarily due to its established link to lung cancer. Dose coefficients are derived from biokinetic models describing the behaviour of radon decay products in the respiratory tract, combined with dosimetric models that account for energy deposition from emitted radiation. Given the variability of environmental and working conditions at different workplaces, obtaining site-specific aerosol data to support more accurate and tailored dose coefficient calculations is beneficial. The key parameters influencing effective dose include the equilibrium equivalent activity concentration (EEAC), total aerosol concentration, and the size distribution of radioactive aerosol particles. Additional factors such as work activity, relative humidity, and ventilation type significantly affect aerosol characteristics and, consequently, the equilibrium factor (F) and the unattached fraction (fp), which can vary considerably between sites. This study presents field measurements of the activity size distribution of short-lived radon progeny at several workplaces, using the Dekati ELPI + cascade impactor and the Graded Screen Array Diffusion Battery (GSA DB). The measurements were conducted primarily at underground workplaces with natural ventilation, including former mining excavations and tourist caves. For comparison, the study also includes one site with forced ventilation-a facility for disposing of low-level radioactive waste-and one outdoor location influenced by radon exhalation from a uranium mining waste rock dump.

• Keywords
• Activity size distribution, Aerosol, Radon, Radon progeny,
• MeSH
• Radon Daughters * analysis   MeSH
• Radiation Monitoring * MeSH
• Workplace MeSH
• Occupational Exposure * statistics & numerical data   analysis   MeSH
• Air Pollutants, Radioactive * analysis   MeSH
• Radon * analysis   MeSH
• Particle Size MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Radon Daughters * MeSH
• Air Pollutants, Radioactive * MeSH
• Radon * MeSH

AIMS: Several methods exist to identify hospital admissions related to adverse drug events (ADEs). Clinical adjudication by healthcare professionals is the gold standard but is labour-intensive. Spontaneous reporting and routinely collected healthcare data using a set of International Classification of Diseases (ICD) codes often underestimate the prevalence of ADE-related admissions. Expanding the set of ICD codes could improve detection; however, validation is limited. The objective was to describe the agreement between ADE-related ICD-10 codes and clinically adjudicated ADE-related admissions in 2 settings. METHODS: This study analysed 2 datasets: 1102 readmissions from a hospital in the Netherlands (180 ADE-related) and 1228 admissions from a hospital in the Czech Republic (195 ADE-related). Clinical adjudication involved expert review including causality assessment to identify ADE-related hospital admissions. The sensitivities and specificities were calculated for a narrow code set (higher drug-likelihood codes containing words like drug-induced) and a broad code set of ICD-10 codes (including codes very likely, likely and possibly ADE-related). RESULTS: The narrow ICD-10 set showed a sensitivity of 3% (95% confidence interval [CI] 2-6%) and a specificity of 99.6% (95% CI 99-100%). The broad set increased sensitivity to 27% (95% CI 23-32%), with specificity decreasing slightly to 92% (95% CI 91-94%). Preventable ADEs were identified less frequently with both ICD-10 code sets. CONCLUSIONS: Only 3% of ADE-related admissions were detected by the narrow ICD-code set and 27% by the broad code set without a significant drop in the specificity. ADE-related ICD codes seem to serve as triggers for 1 in 4 ADE-related hospital admissions.

• Keywords
• adverse drug events, electronic health records, hospitalization, international classification of diseases, pharmacovigilance, preventability,
• MeSH
• Adult MeSH
• Hospitalization * statistics & numerical data   MeSH
• Middle Aged MeSH
• Humans MeSH
• International Classification of Diseases * MeSH
• Drug-Related Side Effects and Adverse Reactions * epidemiology   diagnosis   MeSH
• Patient Admission * statistics & numerical data   MeSH
• Aged MeSH
• Sensitivity and Specificity MeSH
• Adverse Drug Reaction Reporting Systems * MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Validation Study MeSH
• Geographicals
• Czech Republic epidemiology   MeSH
• Netherlands epidemiology   MeSH