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    Utility of First-Morning-Voided Urinary Total Luteinizing Hormone in Detecting the Onset of Central Puberty

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    Introduction: Early morning basal serum luteinizing hormone (S-LH) ≥0.3 IU/L is a specific marker for the onset of central puberty. In this study, we aimed to investigate the sensitivity and specificity of the first-morning-voided (FMV) total urinary LH (U-LH) to replace this marker. Methods: We re-analyzed our previously published data set of 297 children (145 boys and 152 girls, aged 5–15 years, across Tanner stages 1 through 5) using receiver operating characteristic (ROC) analysis and determined cutoff values for FMV total U-LH in predicting early morning S-LH concentration at or above 0.3 IU/L. We also determined S-LH and serum follicle-stimulating hormone (S-FSH) concentrations in girls at different stages of sexual maturation. Results: ROC analysis showed that FMV total U-LH levels of 0.60 and 0.63 IU/L in girls and boys, respectively, predicted early morning S-LH levels of 0.3 IU/L or higher with 97.4% sensitivity and 90.6% specificity. Higher cutoff levels for U-LH (0.78 IU/L for boys and 0.79 IU/L for girls) yielded 94.7% specificity at the expense of a relatively lower level of sensitivity (94.1%). The areas under the curve were 0.98 in boys and 0.99 in girls, respectively. Additionally, the increase in FMV total U-LH (or S-LH) levels identified the activation of central pubertal development at the mean age of 10.3 (10.3) in boys and 10.5 (10.6) in girls. The S-FSH concentrations of the six biochemically prepubertal girls with thelarche, ranging between 2.3 and 2.7 IU/L, were significantly higher than those measured in biochemically and clinically prepubertal girls of the same 10–12-year-old age group and significantly lower than those measured in both biochemically and clinically pubertal girls (p = 0.039 and p = 0.018, respectively). Conclusions: A FMV total U-LH concentration of 0.6 IU/L or above reliably reflects pubertal morning S-LH levels and is effective in detecting the onset of central puberty, which occurs at similar ages in both sexes. Concurrent S-FSH or noninvasive FMV U-FSH determinations may be useful in the differential diagnosis of isolated thelarche.Introduction: Early morning basal serum luteinizing hormone (S-LH) ≥0.3 IU/L is a specific marker for the onset of central puberty. In this study, we aimed to investigate the sensitivity and specificity of the first-morning-voided (FMV) total urinary LH (U-LH) to replace this marker. Methods: We re-analyzed our previously published data set of 297 children (145 boys and 152 girls, aged 5-15 years, across Tanner stages 1 through 5) using receiver operating characteristic (ROC) analysis and determined cutoff values for FMV total U-LH in predicting early morning S-LH concentration at or above 0.3 IU/L. We also determined S-LH and serum follicle-stimulating hormone (S-FSH) concentrations in girls at different stages of sexual maturation. Results: ROC analysis showed that FMV total U-LH levels of 0.60 and 0.63 IU/L in girls and boys, respectively, predicted early morning S-LH levels of 0.3 IU/L or higher with 97.4% sensitivity and 90.6% specificity. Higher cutoff levels for U-LH (0.78 IU/L for boys and 0.79 IU/L for girls) yielded 94.7% specificity at the expense of a relatively lower level of sensitivity (94.1%). The areas under the curve were 0.98 in boys and 0.99 in girls, respectively. Additionally, the increase in FMV total U-LH (or S-LH) levels identified the activation of central pubertal development at the mean age of 10.3 (10.3) in boys and 10.5 (10.6) in girls. The S-FSH concentrations of the six biochemically prepubertal girls with thelarche, ranging between 2.3 and 2.7 IU/L, were significantly higher than those measured in biochemically and clinically prepubertal girls of the same 10-12-year-old age group and significantly lower than those measured in both biochemically and clinically pubertal girls (p = 0.039 and p = 0.018, respectively). Conclusions: A FMV total U-LH concentration of 0.6 IU/L or above reliably reflects pubertal morning S-LH levels and is effective in detecting the onset of central puberty, which occurs at similar ages in both sexes. Concurrent S-FSH or noninvasive FMV U-FSH determinations may be useful in the differential diagnosis of isolated thelarche. </p

    Completed suicide in patients with skin disease:A systematic review and meta-analysis

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    Background: Several skin diseases have been associated with suicidality. However, the term ‘suicidality’ encompasses ideation, which weakens the conclusions. In contrast, the much stronger endpoint of completed suicide and skin disease remains ambiguous. Objective: To determine the risk of completed suicide in adult patients with skin diseases. Methods: The Pubmed, Embase and PsycINFO databases were performed from inception up to June 2023. All original studies in English with a minimum of 10 adult patients that assessed the relationship between a skin disease and death by suicide, were eligible for inclusion. Results: Thirty-seven met the inclusion criteria. Owing to expected interstudy variations, a random effects model was used. A total of 13 skin diseases were identified: 17 population-based high-quality studies, 3,800,748 patients with skin disease, and 33,722,675+ controls were included in the meta-analysis (MA). Each skin disease was analysed separately. Psoriasis: six studies were included in the MA (odds ratio (OR): 1.42, 95% confidence interval (CI) (0.76; 2.68) and found no association. Dermatitis: five studies were included in the MA OR: 1.54, 95% CI (0.57; 4.17) and found no association. Melanoma: four studies were included in the MA, which found an association between melanoma and suicide Standardized mortality rate (SMR): 2.89, 95% CI (1.97; 3.81). Non-melanoma skin cancer: two studies were included in the MA; female patients showed an increased risk of completed suicide compared to the control group SMR: 1.30, 95% CI (1.12; 1.49). In patients with hidradenitis suppurativa, two studies were included in the MA OR: 2.86, 95% CI (1.56; 5.24) and showed a positive association between HS and completed suicide. Conclusions: Suicidality should be considered by physicians when treating dermatological disease, especially when treating patients with hidradenitis suppurativa and melanoma. The association between other skin diseases and completed suicide remains unclear, and further research is indicated.</p

    Morphological differences in myofibre size and shape:A comparative study of the soleus, gastrocnemius, triceps brachii and vastus lateralis in humans and mice

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    Certain skeletal muscles are specialized for their functional roles, yet direct comparisons of cellular morphology of distinct muscles beyond fibre type distribution are limited. This study investigated myofibre morphology in predominantly slow, fast and mixed fibre muscles in humans and mice, with the aim of establishing reference values for muscle-specific myofibre size and shape. Nine healthy young men (Age: 26 ± 1 years, BMI: 23 ± 1 kg/m2) had muscle biopsies taken from soleus, triceps brachii and vastus lateralis muscles. Additionally, the soleus and gastrocnemius muscles were harvested from 7 male C57BL/6 mice. Muscle samples were analysed by ATPase (human) or immunofluorescence (mouse) stainings of fibre type specific cross-sectional area, perimeter and Shape Factor Index (SFI; fibre perimeter2/4 × π × fibre cross-sectional area). In humans, type I fibres had 30%-40% larger CSA and 4%-7% higher SFI in soleus (1.54 ± 0.06) compared to triceps brachii (1.47 ± 0.05) and vastus lateralis (1.43 ± 0.04). Type IIa fibres SFI were 10%-11% higher in soleus (1.61 ± 0.08) compared to triceps brachii (1.45 ± 0.04) and vastus lateralis (1.45 ± 0.08). Soleus type I fibres were more heterogeneous in terms of size and shape compared to other muscles. Analyses of mouse muscle showed a similar pattern, in that CSA and SFI were higher in type I and IIa fibres of the soleus compared to the gastrocnemius. These findings suggest a consistent morphological characteristic of soleus fibres across species, with potentially important implications for future biomedical research.</p

    Motion artifacts and image quality in stroke MRI:associated factors and impact on AI and human diagnostic accuracy

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    Objectives: To assess the prevalence of motion artifacts and the factors associated with them in a cohort of suspected stroke patients, and to determine their impact on diagnostic accuracy for both AI and radiologists. Materials and methods: This retrospective cross-sectional study included brain MRI scans of consecutive adult suspected stroke patients from a non-comprehensive Danish stroke center between January and April 2020. An expert neuroradiologist identified acute ischemic, hemorrhagic, and space-occupying lesions as references. Two blinded radiology residents rated MRI image quality and motion artifacts. The diagnostic accuracy of a CE-marked deep learning tool was compared to that of radiology reports. Multivariate analysis examined associations between patient characteristics and motion artifacts. Results: 775 patients (68 years ± 16, 420 female) were included. Acute ischemic, hemorrhagic, and space-occupying lesions were found in 216 (27.9%), 12 (1.5%), and 20 (2.6%). Motion artifacts were present in 57 (7.4%). Increasing age (OR per decade, 1.60; 95% CI: 1.26, 2.09; p &lt; 0.001) and limb motor symptoms (OR, 2.36; 95% CI: 1.32, 4.20; p = 0.003) were independently associated with motion artifacts in multivariate analysis. Motion artifacts significantly reduced the accuracy of detecting hemorrhage. This reduction was greater for the AI tool (from 88 to 67%; p &lt; 0.001) than for radiology reports (from 100 to 93%; p &lt; 0.001). Ischemic and space-occupying lesion detection was not significantly affected. Conclusion: Motion artifacts are common in suspected stroke patients, particularly in the elderly and patients with motor symptoms, reducing accuracy for hemorrhage detection by both AI and radiologists. Key Points: Question Motion artifacts reduce the quality of MRI scans, but it is unclear which factors are associated with them and how they impact diagnostic accuracy. Findings Motion artifacts occurred in 7% of suspected stroke MRI scans, associated with higher patient age and motor symptoms, lowering hemorrhage detection by AI and radiologists. Clinical relevance Motion artifacts in stroke brain MRIs significantly reduce the diagnostic accuracy of human and AI detection of intracranial hemorrhages. Elderly patients and those with motor symptoms may benefit from a greater focus on motion artifact prevention and reduction.</p

    Emotional-cognitive differences during pregnancy:Adaptations for motherhood

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    Emerging research suggests that unique adaptations in emotional cognition prepare pregnant women for motherhood. This study compared emotional-cognitive responses to infant stimuli in 44 pregnant and 34 non-pregnant Danish participants and explored associations with postpartum outcomes in pregnant participants. Emotional-cognitive responses included facial expressions, skin conductance responses, visual attention, and emotional ratings of multi-modal infant stimuli, including virtual reality. Postpartum outcomes were assessed with questionnaires covering maternal well-being, bonding, reflective functioning, and emotional responses during their own infant cries. Pregnant participants exhibited higher skin conductance responses, more positive facial expressions, and less negative self-reported emotional reactions to infant stimuli compared to non-pregnant participants, with no differences in visual attention. More positive facial expressions to infant faces and vocalizations among pregnant may reflect an adaptive maternal positivity bias, because it correlated with better maternal bonding to their own infant at six months postpartum. Limitations include the cross-sectional design, which makes it difficult to determine whether group differences are pregnancy-driven adaptations, as opposed to findings from alternative longitudinal designs. Nevertheless, the observed differences and positive associations with maternal outcomes are consistent with previous studies, suggesting that pregnancy involves emotional-cognitive adaptations that support the transition to motherhood.</p

    Indonesians would like their coffee produced organically! – Preferences for iced coffee analysed with a discrete choice experiment

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    Indonesia represents a growing yet underrepresented market for sustainably produced coffee, with a limited understanding of how local consumers make purchasing decisions without direct sensory input. While sustainability certifications are widely common on coffee bean products, such information is rarely presented in coffee shops. The study evaluated preferences and willingness-to-pay (WTP) among Indonesian coffee consumers for sustainably produced coffee beverages using a discrete choice experiment (DCE) in a coffee shop setting. Respondents were given choice sets containing three alternatives defined by five attributes: price, type of milk, sugar choice, coffee quality, and sustainability certification. Survey data from 1161 coffee consumers (average age of 28 years old, 75 % female) were segmented using k-means and analysed with mixed logit (MXL) models to account for preference heterogeneity. Three consumer segments were identified: nutritionally conscious consumer (22.8 %), value-oriented hedonist (45.5 %), and sustainable consumer (31.7 %). Our findings reveal a strong preference for sustainability-labelled coffee, particularly with the Organik Indonesia label, followed by plant-based milk, palm sugar, and light-roasted Arabica coffee, with the lowest price of IDR 20,000. Additionally, females, those in the ‘value-oriented hedonist’ segment, and occasional drinkers strongly preferred highly caloric coffee beverages. While price was the least influential attribute in the experiment, we estimated a significant premium for sustainability labels, ranging from 16 % to 22 %, highlighting the positive moral appeal for environmentally and socially responsible products. These findings highlight the positive moral appeal of sustainable products, providing valuable insights for policymakers to promote sustainable coffee consumption in Indonesia.</p

    The Design Law Treaty

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    Protein Distribution in SBA-15:Insights from Thermal Decomposition and Advanced Imaging

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    Ordered Mesoporous Silica (OMS) materials, particularly SBA-15, are widely used in drug delivery due to their structural stability and high porosity. However, the role of macroporosity (pores &gt; 50 nm) in influencing protein adsorption and spatial distribution remains poorly understood. In this study, we produced three SBA-15 variants by changing synthesis temperature and stirring speed, and combined evolved gas analysis (EGA), Raman imaging, and X-ray micro-computed tomography (micro-CT) to investigate the adsorption and distribution of lysozyme, a model protein, in the samples. While thermal analysis showed comparable overall protein uptake across all variants, Raman imaging and micro-CT demonstrated that SBA-15 with the larger macropore distribution exhibited a less uniform lysozyme distribution. These observations suggest that macroporosity affects protein localization within SBA-15, which is critical for optimizing antigen delivery and release. Our results advance understanding of how OMS morphology impacts biomolecule encapsulation, offering insights valuable for the design of advanced drug delivery systems and oral vaccines

    Effect of prenatal high-dose vitamin D on childhood atopic dermatitis is modified by maternal cotinine metabolome:A secondary analysis of a randomized clinical trial

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    Background: Tobacco exposure has been shown to modulate the effect of vitamin D on the risk of atopic diseases. However, randomized clinical trials investigating the potential effect modification between tobacco exposure and vitamin D supplementation on atopic disease risk are lacking. Objective: We sought to investigate the potential effect modification from maternal tobacco exposure on the effect of prenatal high-dose vitamin D supplementation on the risk of child atopic dermatitis, asthma, and allergic rhinitis. Methods: A post hoc analysis in the double-blinded COPSAC2010 randomized clinical trial (NCT00856947) including 581 mother–child pairs randomized to 2800 IU/d (high-dose) versus 400 IU/d (standard-dose) from pregnancy week 24. Maternal blood metabolomic profiling was performed at inclusion, reflecting maternal tobacco exposure using a supervised sparse partial least squares model. Results: We found a significant effect modification from the maternal cotinine metabolome score (Pinteraction &lt; .01) where high-dose vitamin D reduced atopic dermatitis until the age of 6 years in offspring from mothers with highest (fourth quartile) cotinine metabolome score: crude; hazard ratio = 0.46 (0.23-0.93), P = .03, and adjusted for sex, birth season, socioeconomic circumstances, living environment, air pollution, maternal diet, vitamin D levels, and fish oil intervention; hazard ratio = 0.36 (0.15-0.85), P = .02. Similarly, significant effect modification was demonstrated on the risk of asthma (Pinteraction = .03) until the age of 6 years but not allergic rhinitis (Pinteraction = .08) at the age of 6 years. Conclusions: This exploratory study of prespecified randomized clinical trial outcomes demonstrates effect modifications of the maternal tobacco exposure metabolome on the primary preventive effect of prenatal high-dose vitamin D on offspring atopic disease risk, suggesting a potential personalized prevention strategy targeting mothers exposed to tobacco smoking.</p

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