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Topological indices are the numbers that remain constant under graph automorphism. Topological indices describe a network's connectivity, structure, and topological characteristics. These indices have many applications in crisp graphs. However, in many cases, it is observed that some situations can't be described using the idea of crisp graphs. So, to overcome this issue, the need to define topological indices for fuzzy and bipolar fuzzy graphs arises. The F-index, or the Forgotten Index, is a significant topological index. A bipolar fuzzy graph with two opposite-sided opinions of both the edges and vertices measures the impreciseness or uncertainties of the edges and vertices along the positive and negative sides. In this article, we have presented the Forgotten Index for bipolar fuzzy graphs. Then, we have proved some theorems regarding the F-index of numerous types of bipolar fuzzy graphs, such as regular bipolar fuzzy graphs, complete bipolar fuzzy graphs, etc., the bounds of the F-index in bipolar fuzzy graphs, and the relationships of the F-index with other topological indices in bipolar fuzzy graphs. We have applied the proposed topological index, the F-index for bipolar fuzzy graphs, to matrimonial websites to find potential life partners based on compatibility and discussed the application of the Forgotten Index in gene regulatory networks., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

A central problem of geometry is the tiling of space with simple structures. The classical solutions, such as triangles, squares, and hexagons in the plane and cubes and other polyhedra in three-dimensional space are built with sharp corners and flat faces. However, many tilings in Nature are characterized by shapes with curved edges, nonflat faces, and few, if any, sharp corners. An important question is then to relate prototypical sharp tilings to softer natural shapes. Here, we solve this problem by introducing a new class of shapes, the soft cells , minimizing the number of sharp corners and filling space as soft tilings . We prove that an infinite class of polyhedral tilings can be smoothly deformed into soft tilings and we construct the soft versions of all Dirichlet-Voronoi cells associated with point lattices in two and three dimensions. Remarkably, these ideal soft shapes, born out of geometry, are found abundantly in nature, from cells to shells., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

Clinical indications for the Ti-Zr alloy (Roxolid ® ) mini-implants (MDIs) in subjects with narrow ridges are still under review. The aim was to analyze peri-implant and posterior edentulous area strains dependent on the MDI number, splinting status, loading force, and loading position. Six models were digitally designed and printed. Two, three, or four Ti-Zr MDIs, splinted with a bar or unsplinted (single units), supported mandibular overdentures (ODs), loaded with 50-300 N forces unilaterally, bilaterally, and anteriorly. The artificial mucosa thickness was 2 mm. Strain gauges were bonded on the vestibular and oral peri-implant sides of each MDI, and on the posterior edentulous area under the ODs. Loadings were performed through the metal plate placed on ODs' artificial teeth (15 times repeated). Arithmetic means with standard deviations and the significance of the differences (MANOVA, Sheffe post hoc ) were calculated. Different MDI numbers, loading positions, forces, and splinting elicited different peri-implant microstrains. In the two-MDI models, 300 N force during unilateral loading elicited the highest microstrains (almost 3000 εμ on the loaded side), which can jeopardize bone reparation. On the opposite side, >2500 εμ was registered, which represents high strains. During bilateral loadings, microstrains hardly exceeded 2000 εμ, indicating that bilateral chewers or subjects having lower forces can benefit from the two Ti-Zr MDIs, irrespective of splinting. However, in subjects chewing unilaterally, and inducing higher forces (natural teeth antagonists), or bruxers, only two MDIs may not be sufficient to support the OD. By increasing implant numbers, peri-implant strains decrease in both splinted and single-unit MDI models, far beyond values that can interfere with bone reparation, indicating that splinting is not necessary. When the positions of the loading forces are closer to the implant, higher peri-implant strains are induced. Regarding the distal edentulous area, microstrains reached 2000 εμ only during unilateral loadings in the two-MDI models, and all other strains were lower, below 1500 εμ, confirming that implant-supported overdentures do not lead to edentulous ridge atrophy., Competing Interests: The authors declare that this study received partial funding from Institute Straumann AG. The funder was not involved in the study design, collection, analysis, interpretation of data, writing of this article, or decision to submit it for publication.

Enantiospecific effects play an uprising role in chemistry and technical applications. Chiral molecular networks formed by self-assembly processes at surfaces can be imaged by scanning probe microscopy (SPM). Low contrast and high noise in the topography map often interfere with the automatic image analysis using classical methods. The long SPM image acquisition times restrain Artificial Intelligence-based methods requiring large training sets, leaving only tedious manual work, inducing human-dependent errors and biased labeling. By generating realistic looking synthetic images, the acquisition of real datasets is avoided. Two state-of-the-art object detection architectures are trained to localize and classify chiral unit-cells in a regular molecular chiral network formed by self-assembly of linear molecular bricks. The comparison of different architectures and datasets demonstrates that the training on purely synthetic data outperforms models trained using augmented datasets. A Faster R-CNN model trained solely on synthetic data achieved an excellent mean average precision of 99% on real data. Hence this approach and the transfer to real data show high success, also highlighting the high robustness against experimental noise and different zoom levels across the full experimentally reasonable parameter range. The generalizability of this idea is demonstrated by achieving equally high performance on a different structure, too., (© 2024 The Author(s). Small Methods published by Wiley‐VCH GmbH.)

Smart cities rely on a network of sensors to gather real-time data on various environmental factors, including air quality. This paper addresses the challenges of improving the accuracy of low-cost particulate matter sensors (LCPMSs) which can be compromised by environmental conditions, such as high humidity, which is common in many urban areas. Such weather conditions often lead to the overestimation of particle counts due to hygroscopic particle growth, resulting in a potential public concern, although most of the detected particles consist of just water. The paper presents an innovative design for an indicative air-quality measuring station that integrates the particulate matter sensor with a preconditioning subsystem designed to mitigate the impact of humidity. The preconditioning subsystem works by heating the incoming air, effectively reducing the relative humidity and preventing the hygroscopic growth of particles before they reach the sensor. To validate the effectiveness of this approach, parallel measurements were conducted using both preconditioned and non-preconditioned sensors over a period of 19 weeks. The data were analyzed to compare the performance of the sensors in terms of accuracy for PM 1 , PM 2.5 , and PM 10 particles. The results demonstrated a significant improvement in measurement accuracy for the preconditioned sensor, especially in environments with high relative humidity. When the conditions were too severe and both sensors started measuring incorrect values, the preconditioned sensor-measured values were closer to the actual values. Also, the period of measuring incorrect values was shorter with the preconditioned sensor. The results suggest that the implementation of air preconditioning subsystems in LCPMSs deployed in smart cities can provide a cost-effective solution to overcome humidity-related inaccuracies, thereby improving the overall quality of measured air pollution data.

Considering the adaptability and responsiveness of microorganisms to environmental changes, their indicator potential is still not acknowledged in European directives. This comprehensive study examined the changes of microbial communities in sediments and a range of geochemical parameters from pristine and anthropogenically impacted coastal areas in the eastern Adriatic Sea. Various analytical methods found evidence of sediment contamination (high toxicity level, enrichments of metals, tributyltin) in certain areas, leading to the categorization of sediments based on the level of anthropogenic disturbance. Prokaryotes were identified as the most promising group of microbes for further research, with specific bacterial families (Rhodobacteraceae, Ectothiorhodospiraceae, Cyclobacteriaceae) and genera (Boseongicola, B2M28, Subgroup 23, Sva0485, Thiogranum) proposed as potential indicators of environmental status. Finally, predictive models were developed to identify key indicator variables for assessing anthropogenic impact in sediments. This research represents an essential step toward incorporating microbial communities into assessments of benthic environmental health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In this paper, we define the derived category of weak chain U -complexes, and we give a characterization of any weak chain U -complex as an object in the right bounded homotopy category of weak chain U -complexes of projective modules. Then, we show that the homology functor between the category of chain complexes and weak chain U -complexes is a natural isomorphism by constructing an adjoint pair between these two categories., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

From the recent genome assembly NHGRI_mPonAbe1-v2.0_NCBI (GCF_028885655.2) of orangutan chromosome 13, we computed the precise alpha satellite higher-order repeat (HOR) structure using the novel high-precision GRM2023 algorithm with Global Repeat Map (GRM) and Monomer Distance (MD) diagrams. This study rigorously identified alpha satellite HORs in the centromere of orangutan chromosome 13, discovering a novel 59mer HOR-the longest HOR unit identified in any primate to date. Additionally, it revealed the first intertwined sequence of three HORs, 18mer/27mer/45mer HORs, with a common aligned "backbone" across all HOR copies. The major 7mer HOR exhibits a Willard's-type canonical copy, although some segments of the array display significant irregularities. In contrast, the 14mer HOR forms a regular Willard's-type HOR array. Surprisingly, the GRM2023 high-precision analysis of chromosome 13 of human genome assembly T2T-CHM13v2.0 reveals the presence of only a 7mer HOR, despite both the orangutan and human genome assemblies being derived from whole genome shotgun sequences.

Objective: Recent evidence shows that during slow-wave sleep (SWS), the brain is cleared from potentially toxic metabolites, such as the amyloid-beta protein. Poor sleep or elevated cortisol levels can worsen amyloid-beta clearance, potentially leading to the formation of amyloid plaques, a neuropathological hallmark of Alzheimer disease. Here, we explored how nocturnal neural and endocrine activity affects amyloid-beta fluctuations in the peripheral blood., Methods: We acquired simultaneous polysomnography and all-night blood sampling in 60 healthy volunteers aged 20-68 years. Nocturnal plasma concentrations of amyloid-beta-40, amyloid-beta-42, cortisol, and growth hormone were assessed every 20 minutes. Amyloid-beta fluctuations were modeled with sleep stages, (non)oscillatory power, and hormones as predictors while controlling for age and participant-specific random effects., Results: Amyloid-beta-40 and amyloid-beta-42 levels correlated positively with growth hormone concentrations, SWS proportion, and slow-wave (0.3-4Hz) oscillatory and high-band (30-48Hz) nonoscillatory power, but negatively with cortisol concentrations and rapid eye movement sleep (REM) proportion measured 40-100 minutes previously (all t values > |3|, p values < 0.003). Older participants showed higher amyloid-beta-40 levels., Interpretation: Slow-wave oscillations are associated with higher plasma amyloid-beta levels, whereas REM sleep is related to decreased amyloid-beta plasma levels, possibly representing changes in central amyloid-beta production or clearance. Strong associations between cortisol, growth hormone, and amyloid-beta presumably reflect the sleep-regulating role of the corresponding releasing hormones. A positive association between age and amyloid-beta-40 may indicate that peripheral clearance becomes less efficient with age. ANN NEUROL 2024;96:46-60., (© 2024 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Pubertal timing varies considerably and is associated with later health outcomes. We performed multi-ancestry genetic analyses on ~800,000 women, identifying 1,080 signals for age at menarche. Collectively, these explained 11% of trait variance in an independent sample. Women at the top and bottom 1% of polygenic risk exhibited ~11 and ~14-fold higher risks of delayed and precocious puberty, respectively. We identified several genes harboring rare loss-of-function variants in ~200,000 women, including variants in ZNF483, which abolished the impact of polygenic risk. Variant-to-gene mapping approaches and mouse gonadotropin-releasing hormone neuron RNA sequencing implicated 665 genes, including an uncharacterized G-protein-coupled receptor, GPR83, which amplified the signaling of MC3R, a key nutritional sensor. Shared signals with menopause timing at genes involved in DNA damage response suggest that the ovarian reserve might signal centrally to trigger puberty. We also highlight body size-dependent and independent mechanisms that potentially link reproductive timing to later life disease., (© 2024. The Author(s).)

The main goal of this research was to determine whether there is a correlation between adherence to the Mediterranean diet (assessed by the Mediterranean Diet Serving Score (MDSS)) and parameters indicating thyroid gland activity, such as concentration of thyroid-stimulating hormone (TSH), thyroid hormones (free triiodothyronine (fT3), free thyroxine (fT4)), thyroglobulin (Tg), antibodies to thyroid proteins (thyroglobulin antibodies (TgAb) and thyroid peroxidase antibodies (TPOAb)), and calcitonin (CT) in plasma and serum samples. An additional objective was to investigate whether there are differences in the values of the MDSS among clinical groups (euthyroid individuals, euthyroid individuals with positive TgAb and/or TPOAb, and hypothyroid and hyperthyroid participants). This cross-sectional study included 4620 participants over 18 years of age from the islands of Korčula and Vis, and the mainland city of Split. The MDSS was assessed from a food frequency questionnaire (FFQ). MDSS values were significantly higher in females compared to males and showed a positive association with the age of the participants. There was no significant difference in the MDSS values among the examined clinical groups. In the group of subjects with euthyroidism, a significant positive association was found between fT3 and the MDSS, while in the group of subjects with subclinical hypothyroidism, a significant positive association was observed between the MDSS and both fT3 and fT4. CT levels were also positively associated with the MDSS. Considering the significant positive association of the MDSS and both fT3 and fT4 levels in patients with subclinical hypothyroidism, the results of this study could be used to create guidelines for selecting an appropriate, potentially protective diet for these patients.

The application of industrial technologies is undergoing significant changes. Finding the level at which to use efficient cyberphysical systems is perhaps one of the most important technical preparatory tasks in implementing digital manufacturing. Welding technology systems are investigated, and a framework for capturing the data sets required for data-driven manufacturing is developed. To make full autonomy in a manufacturing environment meaningful, formerly isolated groups of equipment need to be organized into a production information system. In our research, a test system is created that can implement a digital virtual interface and achieve new levels of efficiency with a future digital twin system. In the discourse of the study, the technological parameters of welding test pieces were investigated, namely the available measurement data sets of current, and voltage data. In the summary section, most of the tasks and research directions are presented, which can be envisaged as a continuation of the present study. Our study will be followed by further research, already testing a complete digital twin system, thus reaching another milestone on the way to autonomous manufacturing., (© 2024. The Author(s).)

Hypertension affects more than one billion people worldwide. Here we identify 113 novel loci, reporting a total of 2,103 independent genetic signals (P < 5 × 10 -8 ) from the largest single-stage blood pressure (BP) genome-wide association study to date (n = 1,028,980 European individuals). These associations explain more than 60% of single nucleotide polymorphism-based BP heritability. Comparing top versus bottom deciles of polygenic risk scores (PRSs) reveals clinically meaningful differences in BP (16.9 mmHg systolic BP, 95% CI, 15.5-18.2 mmHg, P = 2.22 × 10 -126 ) and more than a sevenfold higher odds of hypertension risk (odds ratio, 7.33; 95% CI, 5.54-9.70; P = 4.13 × 10 -44 ) in an independent dataset. Adding PRS into hypertension-prediction models increased the area under the receiver operating characteristic curve (AUROC) from 0.791 (95% CI, 0.781-0.801) to 0.826 (95% CI, 0.817-0.836, ∆AUROC, 0.035, P = 1.98 × 10 -34 ). We compare the 2,103 loci results in non-European ancestries and show significant PRS associations in a large African-American sample. Secondary analyses implicate 500 genes previously unreported for BP. Our study highlights the role of increasingly large genomic studies for precision health research., (© 2024. The Author(s).)

Aim: Alpha-1-acid glycoprotein (AGP) is a highly glycosylated protein in human plasma and one of the most abundant acute phase proteins in humans. Glycosylation plays a crucial role in its biological functions, and alterations in AGP N-glycome have been associated with various diseases and inflammatory conditions. However, large-scale studies of AGP N-glycosylation in the general population are lacking., Methods: Using recently developed high-throughput glycoproteomic workflow for site-specific AGP N-glycosylation analysis, 803 individuals from the Croatian island of Korcula were analyzed and their AGP N-glycome data associated with biochemical and physiological traits, as well as different environmental factors., Results: After regression analysis, we found that AGP N-glycosylation is strongly associated with sex, somewhat less with age, along with multiple biochemical and physiological traits (e.g. BMI, triglycerides, uric acid, glucose, smoking status, fibrinogen)., Conclusion: For the first time we have extensively explored the inter-individual variability of AGP N-glycome in a general human population, demonstrating its changes with sex, age, biochemical, and physiological status of individuals, providing the baseline for future population and clinical studies., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Unraveling the intricate centromere structure of human chromosomes holds profound implications, illuminating fundamental genetic mechanisms and potentially advancing our comprehension of genetic disorders and therapeutic interventions. This study rigorously identified and structurally analyzed alpha satellite higher-order repeats (HORs) within the centromere of human chromosome 15 in the complete T2T-CHM13 assembly using the high-precision GRM2023 algorithm. The most extensive alpha satellite HOR array in chromosome 15 reveals a novel cascading HOR, housing 429 15mer HOR copies, containing 4-, 7- and 11-monomer subfragments. Within each row of cascading HORs, all alpha satellite monomers are of distinct types, as in regular Willard's HORs. However, different HOR copies within the same cascading 15mer HOR contain more than one monomer of the same type. Each canonical 15mer HOR copy comprises 15 monomers belonging to only 9 different monomer types. Notably, 65% of the 429 15mer cascading HOR copies exhibit canonical structures, while 35% display variant configurations. Identified as the second most extensive alpha satellite HOR, another novel cascading HOR within human chromosome 15 encompasses 164 20mer HOR copies, each featuring two subfragments. Moreover, a distinct pattern emerges as interspersed 25mer/26mer structures differing from regular Willard's HORs and giving rise to a 34-monomer subfragment. Only a minor 18mer HOR array of 12 HOR copies is of the regular Willard's type. These revelations highlight the complexity within the chromosome 15 centromeric region, accentuating deviations from anticipated highly regular patterns and hinting at profound information encoding and functional potential within the human centromere.

Discrete dynamical systems can exhibit complex behavior from the iterative application of straightforward local rules. A famous class of examples comes from cellular automata whose global dynamics are notoriously challenging to analyze. To address this, we relax the regular connectivity grid of cellular automata to a random graph, which gives the class of graph cellular automata. Using the dynamical cavity method and its backtracking version, we show that this relaxation allows us to derive asymptotically exact analytical results on the global dynamics of these systems on sparse random graphs. Concretely, we showcase the results on a specific subclass of graph cellular automata with "conforming nonconformist" update rules, which exhibit dynamics akin to opinion formation. Such rules update a node's state according to the majority within their own neighborhood. In cases where the majority leads only by a small margin over the minority, nodes may exhibit nonconformist behavior. Instead of following the majority, they either maintain their own state, switch it, or follow the minority. For configurations with different initial biases towards one state we identify sharp dynamical phase transitions in terms of the convergence speed and attractor types. From the perspective of opinion dynamics this answers when consensus will emerge and when two opinions coexist almost indefinitely.

The aim of this study was to investigate lifestyle habits in health and non-health science students from the University of Split, Croatia, and to evaluate their association with perceived stress and psychological well-being. We surveyed 783 students during February-March 2021. Hierarchical multiple regression analysis was used in the analysis. Health science students spent less time using screens, were sitting less, slept less, but also showed better compliance with the Mediterranean diet compared to non-health science students (10.6% vs. 5.9%). There were no differences in stress and well-being perception between the two study groups. Female gender, lack of sleep, less daily sitting time, anxiety, and lower optimism were associated with higher stress in non-health science students, while anxiousness and more sitting were found to be significant among health students. Well-being among health science students was positively associated with BMI, having had COVID-19, being refreshed after waking up during working days, Mediterranean diet adherence, health perception, optimism, and quality of life, and negatively with TV time and anxiousness. Shorter sleep duration on non-working days, feeling refreshed after waking up on non-working days, higher quality of life and optimism, and lower anxiousness were associated with higher well-being among non-health students. Identifying unhealthy lifestyle habits in students is essential for implementing targeted interventions to better their health outcomes.

Background: In this priority-setting exercise, we sought to identify leading research priorities needed for strengthening future pandemic preparedness and response across countries., Methods: The International Society of Global Health (ISoGH) used the Child Health and Nutrition Research Initiative (CHNRI) method to identify research priorities for future pandemic preparedness. Eighty experts in global health, translational and clinical research identified 163 research ideas, of which 42 experts then scored based on five pre-defined criteria. We calculated intermediate criterion-specific scores and overall research priority scores from the mean of individual scores for each research idea. We used a bootstrap (n = 1000) to compute the 95% confidence intervals., Results: Key priorities included strengthening health systems, rapid vaccine and treatment production, improving international cooperation, and enhancing surveillance efficiency. Other priorities included learning from the coronavirus disease 2019 (COVID-19) pandemic, managing supply chains, identifying planning gaps, and promoting equitable interventions. We compared this CHNRI-based outcome with the 14 research priorities generated and ranked by ChatGPT, encountering both striking similarities and clear differences., Conclusions: Priority setting processes based on human crowdsourcing - such as the CHNRI method - and the output provided by ChatGPT are both valuable, as they complement and strengthen each other. The priorities identified by ChatGPT were more grounded in theory, while those identified by CHNRI were guided by recent practical experiences. Addressing these priorities, along with improvements in health planning, equitable community-based interventions, and the capacity of primary health care, is vital for better pandemic preparedness and response in many settings., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and declare the following activities and/or relationships: IR is the Co-Editor in Chief, PS is the China Regional Editor, and DA is an Editorial Board Member of the Journal of Global Health. To ensure that any possible conflict of interest relevant to the journal has been addressed, this article was reviewed according to best practice guidelines of international editorial organisations., (Copyright © 2024 by the Journal of Global Health. All rights reserved.)

Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose the following activities and/or relationships: AS and CR were members of the Scottish Government’s CMO COVID-19 Advisory Group and the NERVTAG’s risk stratification subgroup. CR is a member of SPI-M and MHRA vaccine Benefit and Risk Expert Working Group. AS was a member of AstraZeneca’s Thrombotic Thrombocytopenic Advisory Group and is a member of the Scottish Government’s Standing Committee on Pandemics. IR is the adviser to the Government of the Republic of Croatia for COVID-19. All these roles are unremunerated. IR is the co-Editor-in-Chief of the Journal of Global Health.

Background: Sleep deprivation can decrease parental well-being and degrade mental and physical health in parents of children with chronic illness. The aim of this study was to explore the associations of sleep quality, psychological stress perception, and evening salivary cortisol concentration with self-esteem, optimism and happiness in parents of children with type 1 diabetes and developmental disorders compared to parents of healthy, typically developing children., Methods: We studied 196 parents of children with chronic conditions, including autistic spectrum disorder (N = 33), cerebral palsy (N = 18), Down syndrome (N = 33), and diabetes mellitus type 1 (N = 40) and parents of healthy children (N = 72). We evaluated parental sleep quality, evening salivary cortisol levels, self-esteem, optimism and happiness. Multiple linear regression models were used to assess associations between variables., Results: Compared with those of the control group, the parents of children with autistic spectrum disorders had higher evening cortisol concentrations (β = 0.17; p = 0.038) and lower perceptions of happiness (β=-0.17; p = 0.017), while parents of children with type 1 diabetes had disrupted sleep quality (β = 0.25; p = 0.003). Optimism was negatively associated with the evening cortisol concentration (β=-0.18; p = 0.023) and sleep quality index (β=-0.20; p = 0.012)., Conclusions: Public health programs aimed at lifestyle habit improvement, respite care, and relaxation for parents of children with chronic conditions would be useful for improving parental sleep quality, self-esteem, optimism and happiness., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

To date only a fraction of the genetic footprint of thyroid function has been clarified. We report a genome-wide association study meta-analysis of thyroid function in up to 271,040 individuals of European ancestry, including reference range thyrotropin (TSH), free thyroxine (FT4), free and total triiodothyronine (T3), proxies for metabolism (T3/FT4 ratio) as well as dichotomized high and low TSH levels. We revealed 259 independent significant associations for TSH (61% novel), 85 for FT4 (67% novel), and 62 novel signals for the T3 related traits. The loci explained 14.1%, 6.0%, 9.5% and 1.1% of the total variation in TSH, FT4, total T3 and free T3 concentrations, respectively. Genetic correlations indicate that TSH associated loci reflect the thyroid function determined by free T3, whereas the FT4 associations represent the thyroid hormone metabolism. Polygenic risk score and Mendelian randomization analyses showed the effects of genetically determined variation in thyroid function on various clinical outcomes, including cardiovascular risk factors and diseases, autoimmune diseases, and cancer. In conclusion, our results improve the understanding of thyroid hormone physiology and highlight the pleiotropic effects of thyroid function on various diseases., (© 2024. The Author(s).)

Assessing public health intervention strategies is crucial for effectively managing dengue. While numerous studies have explored the impact of dengue interventions on its transmission dynamics, limited research has focused on the combined effects of implementing multiple therapeutic interventions for disease control. This study presents an epidemic model for understanding dengue transmission dynamics, incorporating two critical therapeutic measures: vaccination and treatment of infected individuals. The model is characterized by ordinary differential equations involving seven-state variables. The investigation encompasses both disease-free and endemic equilibria of the model. The findings reveal that the disease-free equilibrium (only) is globally stable when the basic reproduction number is below one. Interestingly, when the vaccine's effectiveness is low, treatment emerges as a more successful approach in reducing dengue cases than vaccination. In contrast, a highly effective vaccine alone significantly curtails dengue occurrences. Moreover, the study introduces an optimal control problem, featuring an objective function integrating two control mechanisms: vaccination and treatment. The analysis strongly suggests that implementing two control strategies outweighs the efficacy of a single approach in effectively mitigating the spread of the disease., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sow et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Uncovering the functional relevance underlying verbal declarative memory (VDM) genome-wide association study (GWAS) results may facilitate the development of interventions to reduce age-related memory decline and dementia., Methods: We performed multi-omics and pathway enrichment analyses of paragraph (PAR-dr) and word list (WL-dr) delayed recall GWAS from 29,076 older non-demented individuals of European descent. We assessed the relationship between single-variant associations and expression quantitative trait loci (eQTLs) in 44 tissues and methylation quantitative trait loci (meQTLs) in the hippocampus. We determined the relationship between gene associations and transcript levels in 53 tissues, annotation as immune genes, and regulation by transcription factors (TFs) and microRNAs. To identify significant pathways, gene set enrichment was tested in each cohort and meta-analyzed across cohorts. Analyses of differential expression in brain tissues were conducted for pathway component genes., Results: The single-variant associations of VDM showed significant linkage disequilibrium (LD) with eQTLs across all tissues and meQTLs within the hippocampus. Stronger WL-dr gene associations correlated with reduced expression in four brain tissues, including the hippocampus. More robust PAR-dr and/or WL-dr gene associations were intricately linked with immunity and were influenced by 31 TFs and 2 microRNAs. Six pathways, including type I diabetes, exhibited significant associations with both PAR-dr and WL-dr. These pathways included fifteen MHC genes intricately linked to VDM performance, showing diverse expression patterns based on cognitive status in brain tissues., Conclusions: VDM genetic associations influence expression regulation via eQTLs and meQTLs. The involvement of TFs, microRNAs, MHC genes, and immune-related pathways contributes to VDM performance in older individuals., (© 2024. The Author(s).)

An arc in F q 2 is a set P ⊂ F q 2 such that no three points of P are collinear. We use the method of hypergraph containers to prove several counting results for arcs. Let A ( q ) denote the family of all arcs in F q 2 . Our main result is the bound | A ( q ) | ≤ 2 ( 1 + o ( 1 ) ) q . This matches, up to the factor hidden in the o (1) notation, the trivial lower bound that comes from considering all subsets of an arc of size q . We also give upper bounds for the number of arcs of a fixed (large) size. Let k ≥ q 2 / 3 ( log q ) 3 , and let A ( q , k ) denote the family of all arcs in F q 2 with cardinality k . We prove that | A ( q , k ) | ≤ ( 1 + o ( 1 ) ) q k . This result improves a bound of Roche-Newton and Warren [12]. A nearly matching lower bound | A ( q , k ) | ≥ q k follows by considering all subsets of size k of an arc of size q ., (© The Author(s) 2024.)

This paper establishes power-saving bounds for Kloosterman sums associated with the long Weyl element for GL ( n ) for arbitrary n ⩾ 3 , as well as for another type of Weyl element of order 2. These bounds are obtained by establishing an explicit representation as exponential sums. As an application we go beyond Sarnak's density conjecture for the principal congruence subgroup of prime level. We also obtain power-saving bounds for all Kloosterman sums on GL ( 4 ) ., Competing Interests: Conflict of interestThe authors declare that there is no conflict of interest., (© The Author(s) 2023.)

Glycans are an essential structural component of immunoglobulin G (IgG) that modulate its structure and function. However, regulatory mechanisms behind this complex posttranslational modification are not well known. Previous genome-wide association studies (GWAS) identified 29 genomic regions involved in regulation of IgG glycosylation, but only a few were functionally validated. One of the key functional features of IgG glycosylation is the addition of galactose (galactosylation), a trait which was shown to be associated with ageing. We performed GWAS of IgG galactosylation (N=13,705) and identified 16 significantly associated loci, indicating that IgG galactosylation is regulated by a complex network of genes that extends beyond the galactosyltransferase enzyme that adds galactose to IgG glycans. Gene prioritization identified 37 candidate genes. Using a recently developed CRISPR/dCas9 system we manipulated gene expression of candidate genes in the in vitro IgG expression system. Upregulation of three genes, EEF1A1, MANBA and TNFRSF13B , changed the IgG glycome composition, which confirmed that these three genes are involved in IgG galactosylation in this in vitro expression system.

Introduction: Educational attainment, widely used in epidemiologic studies as a surrogate for socioeconomic status, is a predictor of cardiovascular health outcomes. Methods: A two-stage genome-wide meta-analysis of low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride (TG) levels was performed while accounting for gene-educational attainment interactions in up to 226,315 individuals from five population groups. We considered two educational attainment variables: "Some College" (yes/no, for any education beyond high school) and "Graduated College" (yes/no, for completing a 4-year college degree). Genome-wide significant ( p < 5 × 10 -8 ) and suggestive ( p < 1 × 10 -6 ) variants were identified in Stage 1 (in up to 108,784 individuals) through genome-wide analysis, and those variants were followed up in Stage 2 studies (in up to 117,531 individuals). Results: In combined analysis of Stages 1 and 2, we identified 18 novel lipid loci (nine for LDL, seven for HDL, and two for TG) by two degree-of-freedom (2 DF) joint tests of main and interaction effects. Four loci showed significant interaction with educational attainment. Two loci were significant only in cross-population analyses. Several loci include genes with known or suggested roles in adipose ( FOXP1, MBOAT4, SKP2, STIM1, STX4 ), brain ( BRI3, FILIP1, FOXP1, LINC00290, LMTK2, MBOAT4, MYO6, SENP6, SRGAP3, STIM1, TMEM167A, TMEM30A ), and liver ( BRI3, FOXP1 ) biology, highlighting the potential importance of brain-adipose-liver communication in the regulation of lipid metabolism. An investigation of the potential druggability of genes in identified loci resulted in five gene targets shown to interact with drugs approved by the Food and Drug Administration, including genes with roles in adipose and brain tissue. Discussion: Genome-wide interaction analysis of educational attainment identified novel lipid loci not previously detected by analyses limited to main genetic effects., Competing Interests: IN is now employed by Celgene. BMP serves on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. SA is employed by and holds equity in 23andMe, Inc. Authors BK, MW, and CGa were employed by Helmholtz Zentrum München. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 de las Fuentes, Schwander, Brown, Bentley, Winkler, Sung, Munroe, Miller, Aschard, Aslibekyan, Bartz, Bielak, Chai, Cheng, Dorajoo, Feitosa, Guo, Hartwig, Horimoto, Kolčić, Lim, Liu, Manning, Marten, Musani, Noordam, Padmanabhan, Rankinen, Richard, Ridker, Smith, Vojinovic, Zonderman, Alver, Boissel, Christensen, Freedman, Gao, Giulianini, Harris, He, Hsu, Kühnel, Laguzzi, Li, Lyytikäinen, Nolte, Poveda, Rauramaa, Riaz, Robino, Sofer, Takeuchi, Tayo, van der Most, Verweij, Ware, Weiss, Wen, Yanek, Zhan, Amin, Arking, Ballantyne, Boerwinkle, Brody, Broeckel, Campbell, Canouil, Chai, Ida Chen, Chen, Chitrala, Concas, de Faire, de Mutsert, de Silva, de Vries, Do, Faul, Fisher, Floyd, Forrester, Friedlander, Girotto, Gu, Hallmans, Heikkinen, Heng, Homuth, Hunt, Ikram, Jacobs, Kavousi, Khor, Kilpeläinen, Koh, Komulainen, Langefeld, Liang, Liu, Liu, Lohman, Mägi, Manichaikul, McKenzie, Meitinger, Milaneschi, Nauck, Nelson, O’Connell, Palmer, Pereira, Perls, Peters, Polašek, Raitakari, Rice, Rice, Rich, Sabanayagam, Schreiner, Shu, Sidney, Sims, Smith, Starr, Strauch, Tai, Taylor, Tsai, Uitterlinden, van Heemst, Waldenberger, Wang, Wei, Wilson, Xuan, Yao, Yu, Yuan, Zhao, Becker, Bonnefond, Bowden, Cooper, Deary, Divers, Esko, Franks, Froguel, Gieger, Jonas, Kato, Lakka, Leander, Lehtimäki, Magnusson, North, Ntalla, Penninx, Samani, Snieder, Spedicati, van der Harst, Völzke, Wagenknecht, Weir, Wojczynski, Wu, Zheng, Zhu, Bouchard, Chasman, Evans, Fox, Gudnason, Hayward, Horta, Kardia, Krieger, Mook-Kanamori, Peyser, Province, Psaty, Rudan, Sim, Smith, van Dam, van Duijn, Wong, Arnett, Rao, Gauderman, Liu, Morrison, Rotter and Fornage.)

Background: Due to their known variation by geography and economic development, we aimed to evaluate the incidence and mortality of colorectal cancer (CRC) in China over the past decades and identify factors associated with CRC among the Chinese population to provide targeted information on disease prevention., Methods: We conducted a systemic review and meta-analysis of epidemiolocal studies on the incidence, mortality, and associated factors of CRC among the Chinese population, extracting and synthesising data from eligible studies retrieved from seven global and Chinese databases. We pooled age-standardised incidence rates (ASIRs) and mortality rates (ASMRs) for each province, subregion, and the whole of China, and applied a joinpoint regression model and annual per cent changes (APCs) to estimate the trends of CRC incidence and mortality. We conducted random-effects meta-analyses to assess the effect estimates of identified associated risk factors., Results: We included 493 articles; 271 provided data on CRC incidence or mortality, and 222 on associated risk factors. Overall, the ASIR of CRC in China increased from 2.75 to 19.39 (per 100 000 person-years) between 1972 and 2019 with a slowed-down growth rate (APC 1  = 5.75, APC 2  = 0.42), while the ASMR of CRC decreased from 12.00 to 7.95 (per 100 000 person-years) between 1974 and 2020 with a slight downward trend (APC = -0.89). We analysed 62 risk factors with synthesized data; 16 belonging to the categories of anthropometrics factors, lifestyle factors, dietary factors, personal histories and mental health conditions were graded to be associated with CRC risk among the Chinese population in the meta-analysis limited to the high-quality studies., Conclusions: We found substantial variation of CRC burden across regions and provinces of China and identified several associated risk factors for CRC, which could help to guide the formulation of targeted disease prevention and control strategies., Registration: PROSPERO: CRD42022346558., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and declare the following activities and relationships: IR is the Co-Editor in Chief of the of the Journal of Global Health. To ensure that any possible conflict of interest relevant to the journal has been addressed, this article was reviewed according to best practice guidelines of international editorial organisations., (Copyright © 2023 by the Journal of Global Health. All rights reserved.)

Background: We noted that there remains some confusion in the health-science literature on reporting sample odds ratios as estimated rate ratios in case-control studies., Methods: We recap historical literature that definitively answered the question of when sample odds ratios (ORs) from a case-control study are consistent estimators for population rate ratios. We use numerical examples to illustrate the magnitude of the disparity between sample ORs in a case-control study and population rate ratios when sufficient conditions for them to be equal are not satisfied., Results: We stress that in a case-control study, sampling controls from those still at risk at the time of outcome event of the index case is not sufficient for a sample OR to be a consistent estimator for an intelligible rate ratio. In such studies, constancy of the exposure prevalence together with constancy of the hazard ratio (HR) (i.e., the instantaneous rate ratio) over time is sufficient for this result if sampling time is not controlled; if time is controlled, constancy of the HR will suffice. We present numerical examples to illustrate how failure to satisfy these conditions adds a small systematic error to sample ORs as estimates of population rate ratios., Conclusions: We recommend that researchers understand and critically evaluate all conditions used to interpret their estimates as consistent for a population parameter in case-control studies., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and declare the following activities and relationships: AS and CR are members of the Scottish Government’s CMO COVID-19 Advisory Group. IR is a member of the Croatian Government’s Scientific Committee on COVID-19 and co-Editor-in-Chief of the Journal of Global Health. AS and CR are members of NERVTAG’s risk stratification subgroup. CR is a member of SPI-M. AS is a member of AstraZeneca’s Thrombotic Thrombocytopenic Advisory Group and the Scottish Government’s Standing Committee on Pandemics. All roles are unremunerated. All other co-authors report no conflict of interests., (Copyright © 2023 by the Journal of Global Health. All rights reserved.)

It is known that the ~ 1.6 kb Neuroblastoma BreakPoint Family (NBPF) repeats are human specific and contributing to cognitive capabilities, with increasing frequency in higher order repeat 3mer HORs (Olduvai triplets). From chimpanzee to modern human there is a discontinuous jump from 0 to ~ 50 tandemly organized 3mer HORs. Here we investigate the structure of NBPF 3mer HORs in the Neanderthal genome assembly of Pääbo et al., comparing it to the results obtained for human hg38.p14 chromosome 1. Our findings reveal corresponding NBPF 3mer HOR arrays in Neanderthals with slightly different monomer structures and numbers of HOR copies compared to humans. Additionally, we compute the NBPF 3mer HOR pattern for the complete telomere-to-telomere human genome assembly (T2T-CHM13) by Miga et al., identifying two novel tandem arrays of NBPF 3mer HOR repeats with 5 and 9 NBPF 3mer HOR copies. We hypothesize that these arrays correspond to novel NBPF genes (here referred to as NBPFA1 and NBPFA2). Further improving the quality of the Neanderthal genome using T2T-CHM13 as a reference would be of great interest in determining the presence of such distant novel NBPF genes in the Neanderthal genome and enhancing our understanding of human evolution., (© 2023. Springer Nature Limited.)

The main characteristics of blockchains, such as security and traceability, have enabled their use in many distinct scenarios, such as the rise of new cryptocurrencies and decentralized applications (dApps). However, part of the information exchanged in the typical blockchain is public, which can lead to privacy issues. To avoid or mitigate these issues, some blockchains are applying mechanisms to deal with data privacy. Trusted execution environments, the basis of confidential computing, and secure multi-party computation are two technologies that can be applied in that sense. In this paper, we analyze seven blockchain technologies that apply mechanisms to improve data privacy. We define seven technical questions related to common requirements for decentralized applications and, to answer each question, we review the available documentation and gather information from chat channels. We briefly present each blockchain technology and the answers to each technical question. Finally, we present a table summarizing the information and showing which technologies are more prominent.

Background: Vitamin A deficiency (VAD) is widely recognised as a major public health concern in low- and middle-income countries (LMICs). Despite various interventions implemented in many countries, a lack of reliable data is hindering progress. We aimed to consolidate available data and quantify estimates of the prevalence of VAD among children ≤18 years in LMICs., Methods: We searched PubMed, Medline and Embase for studies reported the prevalence of VAD or marginal (m)VAD among children. A multilevel mixed-effects meta-regression approach was applied to establish the regression models for VAD and mVAD prevalence. The total numbers of children affected by VAD and mVAD in LMICs in 2019 were separately calculated from the estimated age- and socio-demographic index (SDI)-specific prevalence with their corresponding United Nations Population Division populations projections. We estimated areas of significant public health concern in 165 LMICs using the lower confidence interval (CI) of VAD prevalence., Results: A total of 116 articles from 40 LMICs were retained. In 2019, VAD and mVAD affected 333.95 million (95% CI = 253.00-433.74) and 556.13 million (95% CI = 388.83-767.94) children and adolescents in 165 LMICs, respectively, corresponding to a prevalence of 14.73% (95% CI = 11.16-19.14) and 24.54% (95% CI = 17.15-33.88). The prevalence of both VAD and mVAD was the highest in children aged 0-5 years at 19.53% (95% CI = 15.03-24.91) and 28.22% (95% CI = 20.00-38.24), respectively, with both steadily decreasing to 10.09% (95% CI = 7.44-13.50) and 20.76% (95% CI = 14.16-29.50) in adolescents aged 13-18 years. The prevalence of VAD was significantly higher in the low SDI region at 29.67% (95% CI = 22.67-37.53) compared to 5.17% (95% CI = 3.14-8.43) estimated in the high-middle SDI region. 68 of the 165 LMICs (41.21%) were classified as areas of moderate to severe VAD public health significance., Conclusions: VAD continues to pose a significant public health concern in many low-income settings. Development in LMICs is a crucial factor for VAD, with a disproportionately higher burden in low SDI regions., Registration: This study protocol was registered with PROSPERO, CRD42020220654., Competing Interests: Disclosure of interest: The author completed the ICMJE Disclosure of Interest Form (available on request from the corresponding author) and declare the following activities and relationships: Igor Rudan is co-Editor-in-Chief of the Journal of Global Health. To ensure that any possible conflict of interest relevant to the journal has been addressed, this article was reviewed according to best practice guidelines of international editorial organisations., (Copyright © 2023 by the Journal of Global Health. All rights reserved.)

Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development., (© 2023. The Author(s).)

Background: Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) displays significant potential for applications in cancer research, especially in tumor typing and subtyping. Lung cancer is the primary cause of tumor-related deaths, where the most lethal entities are adenocarcinoma (ADC) and squamous cell carcinoma (SqCC). Distinguishing between these two common subtypes is crucial for therapy decisions and successful patient management., Results: We propose a new algebraic topological framework, which obtains intrinsic information from MALDI data and transforms it to reflect topological persistence. Our framework offers two main advantages. Firstly, topological persistence aids in distinguishing the signal from noise. Secondly, it compresses the MALDI data, saving storage space and optimizes computational time for subsequent classification tasks. We present an algorithm that efficiently implements our topological framework, relying on a single tuning parameter. Afterwards, logistic regression and random forest classifiers are employed on the extracted persistence features, thereby accomplishing an automated tumor (sub-)typing process. To demonstrate the competitiveness of our proposed framework, we conduct experiments on a real-world MALDI dataset using cross-validation. Furthermore, we showcase the effectiveness of the single denoising parameter by evaluating its performance on synthetic MALDI images with varying levels of noise., Conclusion: Our empirical experiments demonstrate that the proposed algebraic topological framework successfully captures and leverages the intrinsic spectral information from MALDI data, leading to competitive results in classifying lung cancer subtypes. Moreover, the framework's ability to be fine-tuned for denoising highlights its versatility and potential for enhancing data analysis in MALDI applications., (© 2023. The Author(s).)

Obstructive sleep apnea (OSA) is a prevalent disease associated with increased risk for cardiovascular and metabolic diseases and shortened lifespan. The aim of this study was to explore the possibility of using N-glycome as a biomarker for the severe form of OSA. Seventy subjects who underwent a whole-night polysomnography/polygraphy and had apnea-hypopnea index (AHI) over 30 were compared to 23 controls (AHI under 5). Plasma samples were used to extract 39 glycan peaks using ultra-high-performance liquid chromatography (UPLC) and 27 IgG peaks using capillary gel electrophoresis (CGE). We also measured glycan age, a molecular proxy for biological aging. Three plasma and one IgG peaks were significant in a multivariate model controlling for the effects of age, sex, and body mass index. These included decreased GP24 (disialylated triantennary glycans as major structure) and GP28 (trigalactosylated, triantennary, disialylated, and trisialylated glycans), and increased GP32 (trisialylated triantennary glycan). Only one IgG glycan peak was significantly increased (P26), which contains biantennary digalactosylated glycans with core fucose. Patients with severe OSA exhibited accelerated biological aging, with a median of 6.9 years more than their chronological age ( p < 0.001). Plasma N-glycome can be used as a biomarker for severe OSA.

Identifying genetic determinants of reproductive success may highlight mechanisms underlying fertility and identify alleles under present-day selection. Using data in 785,604 individuals of European ancestry, we identified 43 genomic loci associated with either number of children ever born (NEB) or childlessness. These loci span diverse aspects of reproductive biology, including puberty timing, age at first birth, sex hormone regulation, endometriosis and age at menopause. Missense variants in ARHGAP27 were associated with higher NEB but shorter reproductive lifespan, suggesting a trade-off at this locus between reproductive ageing and intensity. Other genes implicated by coding variants include PIK3IP1, ZFP82 and LRP4, and our results suggest a new role for the melanocortin 1 receptor (MC1R) in reproductive biology. As NEB is one component of evolutionary fitness, our identified associations indicate loci under present-day natural selection. Integration with data from historical selection scans highlighted an allele in the FADS1/2 gene locus that has been under selection for thousands of years and remains so today. Collectively, our findings demonstrate that a broad range of biological mechanisms contribute to reproductive success., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The previous review of physical activity (PA) among Croatian children and adolescents was conducted a decade ago. Therefore, the aim of this study was to summarize recent evidence on PA of Croatian children and adolescents and associated personal, social, environmental, and policy factors., Methods: Eighteen experts reviewed the available evidence and provided ratings (from the lowest grade "F" to the highest grade "A+") for the 10 Global Matrix indicators. A systematic search with 100 keywords was conducted in Hrčak, PubMed/MEDLINE, Scopus, SPORTDiscus, and Web of Science for documents published from January 01, 2012, to April 15, 2022. We also conducted internet searches and secondary analyses of data (relative frequencies) from 6 studies., Results: After assessing 7562 references, we included 90 publications in the review and 18 studies (83.3% of medium-to-good quality) in evidence synthesis. We found a high prevalence of insufficient PA (especially among girls) and excessive screen time (especially among boys). PA participation of children and adolescents in Croatia has declined over time. The following grades were assigned to the indicators for Croatia: B- for overall PA, C- for organized sport and PA, C for active play, C- for active transportation, D+ for sedentary behavior, inconclusive for physical fitness, D+ for family and peers, B- for school, B- for community and environment, and D+ for government., Conclusions: Coordinated actions are needed across sectors to improve PA promotion, with a focus on increasing PA among girls, reducing sedentary screen time among boys, improving parental support for PA, and further development of national PA policies.

Infectious diseases still threaten global human health, and host genetic factors have been indicated as determining risk factors for observed variations in disease susceptibility, severity, and outcome. We performed a genome-wide meta-analysis on 4624 subjects from the 10,001 Dalmatians cohort, with 14 infection-related traits. Despite a rather small number of cases in some instances, we detected 29 infection-related genetic associations, mostly belonging to rare variants. Notably, the list included the genes CD28, INPP5D, ITPKB, MACROD2, and RSF1, all of which have known roles in the immune response. Expanding our knowledge on rare variants could contribute to the development of genetic panels that could assist in predicting an individual's life-long susceptibility to major infectious diseases. In addition, longitudinal biobanks are an interesting source of information for identifying the host genetic variants involved in infectious disease susceptibility and severity. Since infectious diseases continue to act as a selective pressure on our genomes, there is a constant need for a large consortium of biobanks with access to genetic and environmental data to further elucidate the complex mechanisms behind host-pathogen interactions and infectious disease susceptibility.

Human plasma transferrin (Tf) N-glycosylation has been mostly studied as a marker for congenital disorders of glycosylation, alcohol abuse, and hepatocellular carcinoma. However, inter-individual variability of Tf N-glycosylation is not known, mainly due to technical limitations of Tf isolation in large-scale studies. Here, we present a highly specific robust high-throughput approach for Tf purification from human blood plasma and detailed characterization of Tf N-glycosylation on the level of released glycans by ultra-high-performance liquid chromatography based on hydrophilic interactions and fluorescence detection (HILIC-UHPLC-FLD), exoglycosidase sequencing, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). We perform a large-scale comparative study of Tf and immunoglobulin G (IgG) N-glycosylation analysis in two human populations and demonstrate that Tf N-glycosylation is associated with age and sex, along with multiple biochemical and physiological traits. Observed association patterns differ compared to the IgG N-glycome corroborating tissue-specific N-glycosylation and specific N-glycans' role in their distinct physiological functions., (© 2023. The Author(s).)

We present an algorithm that, given finite diagrams of simplicial sets X ,  A ,  Y , i.e., functors I op → s Set , such that ( X ,  A ) is a cellular pair, dim X ≤ 2 · conn Y , conn Y ≥ 1 , computes the set [ X , Y ] A of homotopy classes of maps of diagrams ℓ : X → Y extending a given f : A → Y . For fixed n = dim X , the running time of the algorithm is polynomial. When the stability condition is dropped, the problem is known to be undecidable. Using Elmendorf's theorem, we deduce an algorithm that, given finite simplicial sets X ,  A ,  Y with an action of a finite group  G , computes the set [ X , Y ] G A of homotopy classes of equivariant maps ℓ : X → Y extending a given equivariant map f : A → Y under the stability assumption dim X H ≤ 2 · conn Y H and conn Y H ≥ 1 , for all subgroups H ≤ G . Again, for fixed n = dim X , the algorithm runs in polynomial time. We further apply our results to Tverberg-type problem in computational topology: Given a k -dimensional simplicial complex  K , is there a map K → R d without r -tuple intersection points? In the metastable range of dimensions, r d ≥ ( r + 1 ) k + 3 , the problem is shown algorithmically decidable in polynomial time when k , d , and  r are fixed., (© The Author(s) 2023.)

Let p ¯ ( n ) denote the overpartition function. In this paper, our primary goal is to study the asymptotic behavior of the finite differences of the logarithm of the overpartition function, i.e., ( - 1 ) r - 1 Δ r log p ¯ ( n ) , by studying the inequality of the following form log ( 1 + C ( r ) n r - 1 / 2 - 1 + C 1 ( r ) n r ) < ( - 1 ) r - 1 Δ r log p ¯ ( n ) < log ( 1 + C ( r ) n r - 1 / 2 ) for n ≥ N ( r ) , where C ( r ) , C 1 ( r ) , and N ( r ) are computable constants depending on the positive integer r , determined explicitly. This solves a problem posed by Wang, Xie and Zhang in the context of searching for a better lower bound of ( - 1 ) r - 1 Δ r log p ¯ ( n ) than 0. By settling the problem, we are able to show that lim n → ∞ ( - 1 ) r - 1 Δ r log p ¯ ( n ) = π 2 ( 1 2 ) r - 1 n 1 2 - r . ., Competing Interests: Conflict of Interest statement:We hereby confirm that there is no conflict of interest in connection with this paper., (© The Author(s) 2022.)

Let p ¯ ( n ) denote the overpartition function. In this paper, we obtain an inequality for the sequence Δ 2 log p ¯ ( n - 1 ) / ( n - 1 ) α n - 1 which states that log ( 1 + 3 π 4 n 5 / 2 - 11 + 5 α n 11 / 4 ) < Δ 2 log p ¯ ( n - 1 ) / ( n - 1 ) α n - 1 < log ( 1 + 3 π 4 n 5 / 2 ) for n ≥ N ( α ) , where α is a non-negative real number, N ( α ) is a positive integer depending on α , and Δ is the difference operator with respect to n . This inequality consequently implies log -convexity of { p ¯ ( n ) / n n } n ≥ 19 and { p ¯ ( n ) n } n ≥ 4 . Moreover, it also establishes the asymptotic growth of Δ 2 log p ¯ ( n - 1 ) / ( n - 1 ) α n - 1 by showing lim n → ∞ Δ 2 log p ¯ ( n ) / n α n = 3 π 4 n 5 / 2 . , (© The Author(s) 2022, corrected publication 2022.)

Given a lattice L ⊆ Z m and a subset A ⊆ R m , we say that a point in A is lonely if it is not equivalent modulo L to another point of  A . We are interested in identifying lonely points for specific choices of L when A is a dilated standard simplex, and in conditions on L which ensure that the number of lonely points is unbounded as the simplex dilation goes to infinity., (© The Author(s) 2022.)

Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery., Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism., Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk., (© 2022. The Author(s).)

During development, thyroid hormones play an important role in eye development, while in adults, some pathological thyroid conditions can affect the normal functioning of the eyes. Thyroid eye disease is the most well-known eye pathology caused by a pathological thyroid condition. Few studies have investigated the association between ocular parameters and thyroid function. Thus, in this study, we aimed to examine whether thyroid activity affects ocular parameters. This cross-sectional study included 4633 healthy adults recruited within the 10,001 Dalmatians project of the Croatian Biobank. The plasma levels of thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), thyroglobulin (Tg), thyroglobulin antibodies (TgAb), and thyroid peroxidase antibodies (TPOAb) were measured by an immunoassay. We determined 20 ocular parameters for each participant (10 for each eye, including corneal radius, corneal thickness, anterior chamber depth, anterior chamber angle, lens thickness, posterior chamber length, axial length, intraocular lens power (IOL), spherical power, and cylinder power). Patients with hyperthyroidism had thicker corneas compared to euthyroid individuals. Corneal thickness was also negatively associated with plasma TSH levels. Intra-ocular lens power was higher in patients with clinical hypothyroidism, while spherical power was higher in euthyroid individuals with positive antibodies compared to euthyroid individuals. Intra-ocular lens power negatively correlated with fT4 levels, while spherical power positively correlated with TgAb, TPOAb, and Tg levels and negatively correlated with TSH levels. The anterior chamber angle was positively associated with plasma TSH levels and TPOAb levels and negatively associated with plasma fT4 levels. These findings suggest an interesting interplay between ophthalmic measures and thyroid status, detectable even in the general adult population.

Background: The eating habits of Generation Z have changed a lot compared to other Generations. It is presumed that influencers significantly influence the choice of diet among Generation Z. This study aimed to investigate Generation Z's opinion about social networks and the influence of communication channels, mostly influencers, on the choice of diet., Subjects and Methods: This study included 178 participants born between 1997-2010. It was conducted using the Google forms questionnaire program. Participants were initially asked demographic questions such as age, gender, and physical activity. These were followed by questions about their eating habits, social networks, and influencers. After the survey, the results were analyzed using TIBCO Statistica™ 14.0.0., Results: Out of 178 participants, 59% were female, and 41% were male. Most respondents (60.6%) declared that they eat healthily, and among several options to choose from, most respondents chose options related to a healthy diet. Respondents who care about healthy food often seek information from influencers on social networks. Respondents who declared that they eat healthy most often believe that influencers are a credible source of information (p=0.019) and follow influencers for motivation (p=0.022) and for the information they share (p=0.009). Respondents who declared that they pay attention to calorie intake more often believe that influencers are a credible source of information (p=0.011)., Conclusion: The results of this study suggest that influencers greatly influence the eating habits of Generation Z and that they are aware of healthy eating habits. Also, those who take care of healthy eating, follow influencers.