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The St. Nicolas House Analysis (SNHA) is a new graph estimation method for detection of extensive interactions among variables. It operates by ranking absolute bivariate correlation coefficients in descending order thereby creating hierarchic association chains. The latter characterizes dependence structures of interacting variables which can be visualized in a corresponding network graph as a chain of end-to-end connected edges representing direct relationships between the connected nodes. The important advantage of this relatively new approach is that it produces less false positive edges resulting from indirect or transitive associations than expected with standard correlation or linear model-based approaches. Here we aim to improve the detection of ramifications in graphs by addition of different data processing layers to SNHA. They include the combinations of the extensions R-squared gaining(RSG) and linear model check(LMC). SNHA together with these so-called extensions were benchmarked against default SNHA and other reference methods available for the programming language R. In the end combinations of RSG, LMC and Bootstrapping improve SNHA performance across different network types, albeit at the cost of longer computation time.

Twenty-seven scientists met for the annual Auxological conference held at Aschau, Germany, to particularly discuss the interaction between social factors and human growth, and to highlight several topics of general interest to the regulation of human growth. Humans are social mammals. Humans show and share personal interests and needs, and are able to strategically adjust size according to social position, with love and hope being prime factors in the regulation of growth. In contrast to Western societies, where body size has been shown to be an important predictor of socioeconomic status, egalitarian societies without formalized hierarchy and material wealth-dependent social status do not appear to similarly integrate body size and social network. Social network structures can be modeled by Monte Carlo simulation. Modeling dominance hierarchies suggests that winner-loser effects play a pivotal role in robust self-organization that transcends the specifics of the individual. Further improvements of the St. Nicolas House analysis using re-sampling/bootstrap techniques yielded encouraging results for exploring dense networks of interacting variables. Customized pediatric growth references, and approaches towards a Digital Rare Disease Growth Chart Library were presented. First attempts with a mobile phone application were presented to investigate the associations between maternal pre-pregnancy overweight, gestational weight gain, and the child’s future motor development. Clinical contributions included growth patterns of individuals with Silver-Russell syndrome, and treatment burden in children with growth hormone deficiency. Contributions on sports highlighted the fallacy inherent in disregarding the biological maturation status when interpreting physical performance outcomes. The meeting explored the complex influence of nutrition and lifestyle on menarcheal age of Lithuanian girls and emphasized regional trends in height of Austrian recruits. Examples of the psychosocial stress caused by the forced migration of modern Kyrgyz children and Polish children after World War II were presented, as well as the effects of nutritional stress during and after World War I. The session concluded with a discussion of recent trends in gun violence affecting children and adolescents in the United States, and aspects of life history theory using the example of "Borderline Personality Disorder." The features of this disorder are consistent with the notion that it reflects a "fast" life history strategy, with higher levels of allostatic load, higher levels of aggression, and greater exposure to both childhood adversity and chronic stress. The results were discussed in light of evolutionary guided research. In all contributions presented here, written informed consent was obtained from all participants in accordance with institutional Human investigation committee guidelines in accordance with the Declaration of Helsinki amended October 2013, after information about the procedures used.

Background: National Health Surveys have been part of national health services in many countries, but their data are summary com- pilations and commonly used only for describing trends in health and living conditions. Aim: Tostatisticallydisclosenetworksofinteractingvariableswithin National Health Survey data. Sample and methods: We used anthropometric, educational, environ- mental and economic information of people of Sikkim, West Bengal, Telangana, and Gujarat, India, obtained by the Fifth Indian National Family Health Survey (NFHS-5). We applied a new statistical approach labeled as “St. Nicholas House Analysis” (SNHA). SNHA ranks absolute bivariate correlation coef- ficients in descending order according to magnitude. The method creates hierarchic “association chains” of correlation coefficients de- fined by sequences where reversing the start and end point does not alter the ordering of elements. Association chains characterize de- pendence structures within networks of extensively interacting variables. Results: SNHA disclosed fundamental differences in the network of anthropometric, educational, environmental and economic variables of the people of Sikkim, and the people of West Ben- gal, Telangana and Gujarat. Whereas relevant interactions among these variables were largely absent in the people of Sikkim, the variables formed characteristic star-shaped networks with wealth quintile and the possession of motorcycles in a strong central position, in the people of West Bengal, Telangana and Gujarat. Conclusion: Depicting association chains within net- works of extensively interacting variables such as health survey data appears to be a promising statisti- cal tool for disentangling the effects of environmen- tal circumstances, education, and social, economic, political and emotional (SEPE) factors on human growth.

The analysis of a dataset collected over 15 years reveals no biological relevance of Nosema ceranae infections for colony losses; hence, N. ceranae is not considered a serious threat for honey bees in the background of Varroa destructor infestations.

Twenty-four scientists met for the annual Auxological conference held at Krobielowice castle, Poland, to discuss the diverse influences of the environment and of social behavior on growth following last year’s focus on growth and public health concerns (Hermanussen et al., 2022b). Growth and final body size exhibit marked plastic responses to ecological conditions. Among the shortest are the pygmoid people of Rampasasa, Flores, Indonesia, who still live under most secluded insular conditions. Genetics and nutrition are usually considered responsible for the poor growth in many parts of this world, but evidence is accumulating on the prominent impact of social embedding on child growth. Secular trends not only in the growth of height, but also in body proportions, accompany the secular changes in the social, economic and political conditions, with major influences on the emotional and educational circumstances under which the children grow up (Bogin, 2021). Aspects of developmental tempo and aspects of sports were discussed, and the impact of migration by the example of women from Bangladesh who grew up in the UK. Child growth was considered in particular from the point of view of strategic adjustments of individual size within the network of its social group. Theoretical considerations on network characteristics were presented and related to the evolutionary conservation of growth regulating hypothalamic neuropeptides that have been shown to link behavior and physical growth in the vertebrate species. New statistical approaches were presented for the evaluation of short term growth measurements that permit monitoring child growth at intervals of a few days and weeks.

The Summer School in Gülpe (Ecological Station of the University of Potsdam) offers an exceptional learning opportunity for students to apply their knowledge and skills to real-world problems. With the guidance of experienced human biologists, statisticians, and programmers, students have the unique chance to analyze their own data and gain valuable insights. This interdisciplinary setting not only bridges different research areas but also leads to highly valuable outputs. The progress of students within just a few days is truly remarkable, especially when they are motivated and receive immediate feedback on their questions, problems, and results. The Summer School covers a wide range of topics, with this year’s focus mainly on two areas: understanding the impact of socioeconomic and physiological factors on human development and mastering statistical techniques for analyzing data such as changepoint analysis and the St. Nicolas House Analysis (SNHA) to visualize interacting variables. The latter technique, born out of the Summer School’s emphasis on gaining comprehensive data insights and understanding major relationships, has proven to be a valuable tool for researchers in the field. The articles in this special issue demonstrate that the Summer School in Gülpe stands as a testament to the power of practical learning and collaboration. Students who attend not only gain hands-on experience but also benefit from the expertise of professionals and the opportunity to engage with peers from diverse disciplines.

The St. Nicolas House algorithm (SNHA) finds association chains of direct dependent variables in a data set. The dependency is based on the correlation coefficient, which is visualized as an undirected graph. The network prediction is improved by a bootstrap routine. It enables the computation of the empirical p-value, which is used to evaluate the significance of the predicted edges. Synthetic data generated with the Monte Carlo method were used to firstly compare the Python package with the original R package, and secondly to evaluate the predicted network using the sensitivity, specificity, balanced classification rate and the Matthew's correlation coefficient (MCC). The Python implementation yields the same results as the R package. Hence, the algorithm was correctly ported into Python. The SNHA scores high specificity values for all tested graphs. For graphs with high edge densities, the other evaluation metrics decrease due to lower sensitivity, which could be partially improved by using bootstrap,while for graphs with low edge densities the algorithm achieves high evaluation scores. The empirical p-values indicated that the predicted edges indeed are significant.

Seventeen scientists met for this year’s conference on Auxology held at Krobielowice castle, Poland, to discuss growth and public health concerns. The regulation of growth is complex and besides metabolic and endocrine components including hypothalamic releasing factors, growth hormone and multiple downstream effectors, comprises the full spectrum of the psychosocial, economic and emotional environment including signaling dominance, competence, prestige, or subordination and indulgence, all of this being sensitive to urban or rural lifestyle, the political climate and with marked plasticity throughout history. New statistical techniques (St. Nicolas House Analysis) are presented for analyzing anthropometric variables for public health concerns. The impact of spatial differences on developmental tempo, growth in height, and the prevalence of childhood obesity are discussed as well as the impact of social mobility on obesity, and the benefits of the biopsychosocial status when getting along with socio-economic disasters and the COVID-19 pandemic.

Background: Critical cut-off values of BMI-for-age z-scores (BAZ) are used to define “thinness”, “overweight” and “obesity”, but the validity of these cut-off values needs to be questioned in populations that are shorter or taller than the reference. We hypothesized that the prevalence of thinness, overweight, and obesity depends on population height and performed a random simulation. Methods: We created virtual child populations aged 2-10 years with normally distributed height expressed as height-for-age z-scores (HAZ) and weight expressed as weight-for-age z-score (WAZ), based on WHO growth standards and references, with a correlation r=0.7 between height and weight. We adjusted weight-for-height and calculated BAZ. Results: BAZ depends on height and age. In short children (mean HAZ=-2 to HAZ=-3), the prevalence of thinness falls to less than 1% in the youngest and rises up to 10% (mean HAZ=-2) and up to 13% (mean HAZ=-3) at age 10 years. The prevalence of obesity rises to up to 7% in the shortest and youngest and falls close to zero at age 10. Short young children and tall older children are more prone to be misclassified as overweight. Conclusions: The prevalence of thinness, overweight and obesity depends on height and age. The coexistence of being short and being overweight – currently referred to as “double burden of malnutrition” – needs consideration as to what extent this condition is a health issue or reflects calculation artefacts. The arithmetic dilemma particularly affects young children in short populations. We suggest abstaining from defining “thinness”, “overweight”, or “obesity” by BMI z-scores. Different states of under- and malnutrition should rather be classified by direct or indirect measures of body fat.

Background: Network models are useful tools for researchers to simplify and understand investigated systems. Yet, the assessment of methods for network construction is often uncertain. Random resampling simulations can aid to assess methods, provided synthetic data exists for reliable network construction. Objectives: We implemented a new Monte Carlo algorithm to create simulated data for network reconstruction, tested the influence of adjusted parameters and used simulations to select a method for network model estimation based on real-world data. We hypothesized, that reconstructs based on Monte Carlo data are scored at least as good compared to a benchmark. Methods: Simulated data was generated in R using the Monte Carlo algorithm of the mcgraph package. Benchmark data was created by the huge package. Networks were reconstructed using six estimator functions and scored by four classification metrics. For compatibility tests of mean score differences, Welch’s t-test was used. Network model estimation based on real-world data was done by stepwise selection. Samples: Simulated data was generated based on 640 input graphs of various types and sizes. The real-world dataset consisted of 67 medieval skeletons of females and males from the region of Refshale (Lolland) and Nordby (Jutland) in Denmark. Results: Results after t-tests and determining confidence intervals (CI95%) show, that evaluation scores for network reconstructs based on the mcgraph package were at least as good compared to the benchmark huge. The results even indicate slightly better scores on average for the mcgraph package. Conclusion: The results confirmed our objective and suggested that Monte Carlo data can keep up with the benchmark in the applied test framework. The algorithm offers the feature to use (weighted) un- and directed graphs and might be useful for assessing methods for network construction.

Recently, mass cytometry has enabled quantification of up to 50 parameters for millions of cells per sample. It remains a challenge to analyze such high-dimensional data to exploit the richness of the inherent information, even though many valuable new analysis tools have already been developed. We propose a novel algorithm “pattern recognition of immune cells (PRI)” to tackle these high-dimensional protein combinations in the data. PRI is a tool for the analysis and visualization of cytometry data based on a three or more-parametric binning approach, feature engineering of bin properties of multivariate cell data, and a pseudo-multiparametric visualization. Using a publicly available mass cytometry dataset, we proved that reproducible feature engineering and intuitive understanding of the generated bin plots are helpful hallmarks for re-analysis with PRI. In the CD4+T cell population analyzed, PRI revealed two bin-plot patterns (CD90/CD44/CD86 and CD90/CD44/CD27) and 20 bin plot features for threshold-independent classification of mice concerning ineffective and effective tumor treatment. In addition, PRI mapped cell subsets regarding co-expression of the proliferation marker Ki67 with two major transcription factors and further delineated a specific Th1 cell subset. All these results demonstrate the added insights that can be obtained using the non-cluster-based tool PRI for re-analyses of high-dimensional cytometric data.

Twenty-one scientists met for this year’s virtual conference on Auxology held at the University Potsdam, Germany, to discuss child and adolescent growth during times of fear and emotional stress. Growth within the broad range of normal for age and sex is considered a sign of good general health whereas fear and emotional stress can lead to growth faltering. Stunting is a sign of social disadvantage and poor parental education. Adverse childhood experiences affect child development, particularly in families with low parental education and low socioeconomic status. Negative effects were also shown in Indian children exposed prenatally and in early postnatal life to the cyclone Aila in 2009. Distrust, fears and fake news regarding the current Corona pandemic received particular attention though the effects generally appeared weak. Mean birth weight was higher; rates of low, very and extremely low birth weight were lower. Other topics discussed by the participants, were the influences of economic crises on birth weight, the measurement of self-confidence and its impact on growth, the associations between obesity, peer relationship, and behavior among Turkish adolescents, height trends in Indonesia, physiological neonatal weight loss, methods for assessing biological maturation in sportsmen, and a new method for skeletal age determination. The participants also discussed the association between acute myocardial infarction and somatotype in Estonia, rural-urban growth differences in Mongolian children, socio-environmental conditions and sexual dimorphism, biological mortality bias, and new statistical techniques for describing inhomogeneity in the association of bivariate variables, and for detecting and visualizing extensive interactions among variables.

Twenty-three scientists met at Krobielowice, Poland to discuss the role of growth, nutrition and economy on body size. Contrasting prevailing concepts, re-analyses of studies in Indonesian and Guatemalan school children with high prevalence of stunting failed to provide evidence for an association between nutritional status and body height. Direct effects of parental education on growth that were not transmitted via nutrition were shown in Indian datasets using network analysis and novel statistical methods (St. Nicolas House Analysis) that translate correlation matrices into network graphs. Data on Polish children suggest significant impact of socioeconomic sensitivity on child growth, with no effect of maternal money satisfaction. Height and maturation tempo affect the position of a child among its peers. Correlations also exist between mood disorders and height. Secular changes in height and weight varied across decades independent of population size. Historic and recent Russian data showed that height of persons whose fathers performed manual work were on average four cm shorter than persons whose fathers were high-degree specialists. Body height, menarcheal age, and body proportions are sensitive to socioeconomic variables. Additional topics included delayed motherhood and its associations with newborn size; geographic and socioeconomic indicators related to low birth weight, prematurity and stillbirth rate; data on anthropometric history of Brazil, 1850-1950; the impact of central nervous system stimulants on the growth of children with attention-deficit/hyperactivity disorder; and pituitary development and growth hormone secretion. Final discussions debated on reverse causality interfering between social position, and adolescent growth and developmental tempo.

Dysregulated cytokine expression by T cells plays a pivotal role in the pathogenesis of autoimmune diseases. However, the identification of the corresponding pathogenic subpopulations is a challenge, since a distinction between physiological variation and a new quality in the expression of protein markers requires combinatorial evaluation. Here, we were able to identify a super-functional follicular helper T cell (Tfh)-like subpopulation in lupus-prone NZBxW mice with our binning approach "pattern recognition of immune cells (PRI)". PRI uncovered a subpopulation of IL-21+ IFN-γhigh PD-1low CD40Lhigh CXCR5- Bcl-6- T cells specifically expanded in diseased mice. In addition, these cells express high levels of TNF-α and IL-2, and provide B cell help for IgG production in an IL-21 and CD40L dependent manner. This super-functional T cell subset might be a superior driver of autoimmune processes due to a polyfunctional and high cytokine expression combined with Tfh-like properties.

Abstract Background The unisexual Amazon molly (Poecilia formosa) originated from a hybridization between two sexual species, the sailfin molly (Poecilia latipinna) and the Atlantic molly (Poecilia mexicana). The Amazon molly reproduces clonally via sperm-dependent parthenogenesis (gynogenesis), in which the sperm of closely related species triggers embryogenesis of the apomictic oocytes, but typically does not contribute genetic material to the next generation. We compare for the first time the gonadal transcriptome of the Amazon molly to those of both ancestral species, P. mexicana and P. latipinna. Results We sequenced the gonadal transcriptomes of the P. formosa and its parental species P. mexicana and P. latipinna using Illumina RNA-sequencing techniques (paired-end, 100 bp). De novo assembly of about 50 million raw read pairs for each species was performed using Trinity, yielding 106,922 transcripts for P. formosa, 115,175 for P. latipinna, and 133,025 for P. mexicana after eliminating contaminations. On the basis of sequence similarity comparisons to other teleost species and the UniProt databases, functional annotation, and differential expression analysis, we demonstrate the similarity of the transcriptomes among the three species. More than 40% of the transcripts for each species were functionally annotated and about 70% were assigned to orthologous genes of a closely related species. Differential expression analysis between the sexual and unisexual species uncovered 2035 up-regulated and 564 down-regulated genes in P. formosa. This was exemplary validated for six genes by qRT-PCR. Conclusions We identified more than 130 genes related to meiosis and reproduction within the apomictically reproducing P. formosa. Overall expression of these genes seems to be down-regulated in the P. formosa transcriptome compared to both ancestral species (i.e., 106 genes down-regulated, 29 up-regulated). A further 35 meiosis and reproduction related genes were not found in the P. formosa transcriptome, but were only expressed in the sexual species. Our data support the hypothesis of general down-regulation of meiosis-related genes in the apomictic Amazon molly. Furthermore, the obtained dataset and identified gene catalog will serve as a resource for future research on the molecular mechanisms behind the reproductive mode of this unisexual species.

The Western honey bee (Apis mellifera) is widely used as commercial pollinator in worldwide agriculture and, therefore, plays an important role in global food security. Among the parasites and pathogens threatening health and survival of honey bees are two species of microsporidia, Nosema apis and Nosema ceranae. Nosema ceranae is considered an emerging pathogen of the Western honey bee. Reports on the spread of N. ceranae suggested that this presumably highly virulent species is replacing its more benign congener N. apis in the global A. mellifera population. We here present a 12 year longitudinal cohort study on the prevalence of N. apis and N. ceranae in Northeast Germany. Between 2005 and 2016, a cohort of about 230 honey bee colonies originating from 23 apiaries was sampled twice a year (spring and autumn) resulting in a total of 5,600 bee samples which were subjected to microscopic and molecular analysis for determining the presence of infections with N. apis or/and N. ceranae. Throughout the entire study period, both N. apis- and N. ceranae-infections could be diagnosed within the cohort. Logistic regression analysis of the prevalence data demonstrated a significant increase of N. ceranae-infections over the last 12 years, both in autumn (reflecting the development during the summer) and in spring (reflecting the development over winter) samples. Cell culture experiments confirmed that N. ceranae has a higher proliferative potential than N. apis at 27° and 33°C potentially explaining the increase in N. ceranae prevalence during summer. In autumn, characterized by generally low infection prevalence, this increase was accompanied by a significant decrease in N. apis-infection prevalence. In contrast, in spring, the season with a higher prevalence of infection, no significant decrease of N. apis infections despite a significant increase in N. ceranae infections could be observed. Therefore, our data do not support a general advantage of N. ceranae over N. apis and an overall replacement of N. apis by N. ceranae in the studied honey bee population.