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We provide an overview of the status of Monte-Carlo event generators for high-energy particle physics. Guided by the experimental needs and requirements, we highlight areas of active development, and opportunities for future improvements. Particular emphasis is given to physics models and algorithms that are employed across a variety of experiments. These common themes in event generator development lead to a more comprehensive understanding of physics at the highest energies and intensities, and allow models to be tested against a wealth of data that have been accumulated over the past decades. A cohesive approach to event generator development will allow these models to be further improved and systematic uncertainties to be reduced, directly contributing to future experimental success. Event generators are part of a much larger ecosystem of computational tools. They typically involve a number of unknown model parameters that must be tuned to experimental data, while maintaining the integrity of the underlying physics models. Making both these data, and the analyses with which they have been obtained accessible to future users is an essential aspect of open science and data preservation. It ensures the consistency of physics models across a variety of experiments.

Aiming to offer a diagnostic tool to aid examiners with correct hip typing and decision-making about patient management, members of the Board of the International Interdisciplinary Consensus Committee on DDH Evaluation (ICODE – https://www.icode.expert), introduced the cross-platform mobile application (Android and iOS) called “ICODE Hip US Calculator”.

In the article, emphasis is put on the modern artificial neural network structure, which in the literature is known as a deep neural network. Network includes more than one hidden layer and comprises many standard modules with ReLu nonlinear activation function. A learning algorithm includes two standard steps, forward and backward, and its effectiveness depends on the way the learning error is transported back through all the layers to the first layer. Taking into account all the dimensionalities of matrixes and the nonlinear characteristics of ReLu activation function, the problem is very difficult from a theoretic point of view. To implement simple assumptions in the analysis, formal formulas are used to describe relations between the structure of every layer and the internal input vector. In practice tasks, neural networks’ internal layer matrixes with ReLu activations function, include a lot of null value of weight coefficients. This phenomenon has a negatives impact on the effectiveness of the learning algorithm convergences. A theoretical analysis could help to build more effective algorithms.

Purpose: The aim of our study was to use the chondro-osseous border (COB) as an indispensable assessment criterion to evaluate the quality of baby hip ultrasonography (US) images in the literature pertaining to the application of Graf's technique., Materials and Methods: Our literature review search yielded 144 articles. Of these, 41 contained images that were stated to be based on the application of Graf's technique. Two reviewers, a radiologist and an orthopaedic surgeon, both course instructors for the use of baby hip US for developmental dysplasia of the hip (DDH), independently evaluated the articles to assess the diagnostic validity of the published images on the basis of a single criterion: the identification of the COB., Results: Of the 41 articles which were analyzed, 15 contained images without a COB, which corresponds to 36% (roughly, one out of three). Articles from countries where universal screening is performed (Germany, Italy, Switzerland, Mongolia) were all correct. All the articles from Turkey, a country which has made significant contribution with published material about Graf's technique over many years, and most of the articles from China (80%), where Graf's technique has become popular in recent years, contained correct images., Conclusion: Published literature lacks strict criteria for the publication of correct images corresponding to Graf's technique in baby hip US. This fact raises concerns about the quality of published material (and, as a corollary, the quality of clinical application of the technique) and should have ramifications on scientific journal policies regarding the publication of such manuscripts., (© 2023. Società Italiana di Ultrasonologia in Medicina e Biologia (SIUMB).)

Since the publication of Professor Reinhard Graf's work in 1980, Graf's technique has become the gold standard for screening Developmental Dysplasia of the Hip (DDH) in many European and non-European countries. Despite the fact that it is supported by robust literature evidence, there is criticism about its reliability and reproducibility, questioning severalaspects of the diagnostic procedure. There is, however, concern, based on recent literature, about the quality and reliability of the published data, which may, in many cases, be based on inadequate scans, and therefore any conclusions drawn have to be questioned. The aim of this review is to demonstrate the most important aspects of Graf's technique, to clarify the potential sources of confusion and to flag up the most common errors and mistakes made, either during the ultrasound examination, or during the reporting procedure. Furthermore, this review can be used as a guide for reviewers and editors and should help to enhance the quality control of publications on this subject.

Introduction: The method of infant hip sonography according to Graf is used for general hip screening in Serbia, Austria, and Germany and is considered the gold standard. In other countries, such as the USA, however, it is not well accepted and is claimed to lead to high costs and overtreatment. The aim of this study was to investigate how many of the mentioned sources in a recent review article contained sonograms that met the quality criteria as taught in Graf's ultrasound courses., Methods: A systematic review published by Sakkers et al. was analyzed in terms of addressing the quality criteria of Graf's method. Studies that were suitable by title, abstract, manuscript, that contained an image of sonographic hip examination, and that were accessible were included into analysis., Results: Within the described review, there were 22 papers on the Graf method. Of these, 10 contained hip sonograms and were applicable for final analysis. The quality criteria according to Graf were not fulfilled within 5 of these 10 papers. Within these papers, there are examples of schematic sonograms that do not correspond with the quality criteria either., Conclusion: Skepticism regarding the Graf method may be based on user errors and insufficient application of the Graf quality assessment algorithm, which results in high intra- and inter-observer variations. Based on these findings, a working group was initiated to evaluate further work according to the same procedure (currently approximately 130 papers)., Competing Interests: The 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., (© 2022 Ossendorff, Placzek, Bornemann and Walter.)

Purpose: Sonographic hip examination according to Graf is widely accepted standard for diagnosing developmental dysplastic hips (DDH) but it is criticized for alleged intra- and interobserver variations. This review was conducted to evaluate whether objective quality criteria according to the Graf method are fulfilled within scientific literature., Methods: A systematic literature search on Pubmed was performed using the search string: [(DDH) OR (Hip dysplasia)] AND (Graf). Studies suitable by title, abstract, manuscript, containing an image of sonographic hip examination and online accessibility were included into analysis., Results: 131 studies were included into final analysis. Only 68 (51.9%) presented correct sonographic images according Graf's criteria. 98 (74.8%) studies plotted alpha-angles (angle between bony roof line and base line) but only 85 (64.8%) studies beta-angles (angle between cartilage roof line and base line). Studies were contributed from 25 countries., Conclusion: Assumingly, skepticism regarding the Graf method is based on user errors and insufficient application of the Graf quality assessment algorithm resulting in high intra- and interobserver variations. When performed correctly, the Graf method is of high diagnostic value., Competing Interests: The 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 © 2022 Walter, Ossendorff, Yagdiran, Hockmann, Bornemann and Placzek.)

In September 2018, an international meeting of doctors of various disciplines, with expertise in the detection and treatment of DDH, was held in Csolyospalos, Hungary. The aim was to achieve consensus on the detection and early treatment of the condition and to develop a standardized system of teaching and training for hip ultrasound. There was strong agreement that US screening is essential. Specifically the Graf technique was selected as the technique of choice. Universal US screening was strongly favored. Screening should be carried out as soon as possible, but not later than the sixth week of age. US screening is cost-effective, does not result in overtreatment, and contributes to a reduction of long-term consequences. The essential principle of treatment is timely application of a device to achieve reduction, retention and maturation, by holding the hips in flexion, and a safe degree of abduction. It was agreed that the effectiveness of any screening policy depends on the correct scanning technique. Therefore, standardization of teaching and training of the Graf technique is mandatory. A unified teaching policy and materials should be developed for this purpose. Certification, re-certification and audit were discussed. The group, which has been formalized as the International Interdisciplinary Consensus Committee On DDH Evaluation (ICODE), will continue to meet and work towards establishing international consensus on DDH, standardizing and developing teaching and training of the Graf technique for hip US, and maintaining standards for detection and management., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

The BRENDA enzyme database (www.brenda-enzymes.org), recently appointed ELIXIR Core Data Resource, is the main enzyme and enzyme-ligand information system. The core database provides a comprehensive overview on enzymes. A collection of 4.3 million data for ∼84 000 enzymes manually evaluated and extracted from ∼140 000 primary literature references is combined with information obtained by text and data mining, data integration and prediction algorithms. Supplements comprise disease-related data, protein sequences, 3D structures, predicted enzyme locations and genome annotations. Major developments are a revised ligand summary page and the structure search now including a similarity and isomer search. BKMS-react, an integrated database containing known enzyme-catalyzed reactions, is supplemented with further reactions and improved access to pathway connections. In addition to existing enzyme word maps with graphical information of enzyme specific terms, plant word maps have been developed. They show a graphical overview of terms, e.g. enzyme or plant pathogen information, connected to specific plants. An organism summary page showing all relevant information, e.g. taxonomy and synonyms linked to enzyme data, was implemented. Based on a decision by the IUBMB enzyme task force the enzyme class EC 7 has been established for 'translocases', enzymes that catalyze a transport of ions or metabolites across cellular membranes.

Epithelial organoids are simplified models of organs grown in vitro from embryonic and adult stem cells. They are widely used to study organ development and disease, and enable drug screening in patient-derived primary tissues. Current protocols, however, rely on animal- and tumor-derived basement membrane extract (BME) as a 3D scaffold, which limits possible applications in regenerative medicine. This prompted us to study how organoids interact with their matrix, and to develop a well-defined hydrogel that supports organoid generation and growth. It is found that soft fibrin matrices provide suitable physical support, and that naturally occurring Arg-Gly-Asp (RGD) adhesion domains on the scaffold, as well as supplementation with laminin-111, are key parameters required for robust organoid formation and expansion. The possibility to functionalize fibrin via factor XIII-mediated anchoring also allows to covalently link fluorescent nanoparticles to the matrix for 3D traction force microscopy. These measurements suggest that the morphogenesis of budding intestinal organoids results from internal pressure combined with higher cell contractility in the regions containing differentiated cells compared to the regions containing stem cells. Since the fibrin/laminin matrix supports long-term expansion of all tested murine and human epithelial organoids, this hydrogel can be widely used as a defined equivalent to BME., (© 2018 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The BRENDA enzyme database (www.brenda-enzymes.org) has developed into the main enzyme and enzyme-ligand information system in its 30 years of existence. The information is manually extracted from primary literature and extended by text mining procedures, integration of external data and prediction algorithms. Approximately 3 million data from 83 000 enzymes and 137 000 literature references constitute the manually annotated core. Text mining procedures extend these data with information on occurrence, enzyme-disease relationships and kinetic data. Prediction algorithms contribute locations and genome annotations. External data and links complete the data with sequences and 3D structures. A total of 206 000 enzyme ligands provide functional and structural data. BRENDA offers a complex query tool engine allowing the users an efficient access to the data via different search methods and explorers. The new design of the BRENDA entry page and the enzyme summary pages improves the user access and the performance. New interactive and intuitive BRENDA pathway maps give an overview on biochemical processes and facilitate the visualization of enzyme, ligand and organism information in the biochemical context. SCOPe and CATH, databases for protein structure classification, are included. New online and video tutorials provide online training for the users. BRENDA is freely available for academic users., (© The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.)

The BRENDA enzyme information system (http://www.brenda-enzymes.org/) has developed into an elaborate system of enzyme and enzyme-ligand information obtained from different sources, combined with flexible query systems and evaluation tools. The information is obtained by manual extraction from primary literature, text and data mining, data integration, and prediction algorithms. Approximately 300 million data include enzyme function and molecular data from more than 30,000 organisms. The manually derived core contains 3 million data from 77,000 enzymes annotated from 135,000 literature references. Each entry is connected to the literature reference and the source organism. They are complemented by information on occurrence, enzyme/disease relationships from text mining, sequences and 3D structures from other databases, and predicted enzyme location and genome annotation. Functional and structural data of more than 190,000 enzyme ligands are stored in BRENDA. New features improving the functionality and analysis tools were implemented. The human anatomy atlas CAVEman is linked to the BRENDA Tissue Ontology terms providing a connection between anatomical and functional enzyme data. Word Maps for enzymes obtained from PubMed abstracts highlight application and scientific relevance of enzymes. The EnzymeDetector genome annotation tool and the reaction database BKM-react including reactions from BRENDA, KEGG and MetaCyc were improved. The website was redesigned providing new query options., (© The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.)

The BRENDA (BRaunschweig ENzyme DAtabase) enzyme portal (http://www.brenda-enzymes.org) is the main information system of functional biochemical and molecular enzyme data and provides access to seven interconnected databases. BRENDA contains 2.7 million manually annotated data on enzyme occurrence, function, kinetics and molecular properties. Each entry is connected to a reference and the source organism. Enzyme ligands are stored with their structures and can be accessed via their names, synonyms or via a structure search. FRENDA (Full Reference ENzyme DAta) and AMENDA (Automatic Mining of ENzyme DAta) are based on text mining methods and represent a complete survey of PubMed abstracts with information on enzymes in different organisms, tissues or organelles. The supplemental database DRENDA provides more than 910 000 new EC number-disease relations in more than 510 000 references from automatic search and a classification of enzyme-disease-related information. KENDA (Kinetic ENzyme DAta), a new amendment extracts and displays kinetic values from PubMed abstracts. The integration of the EnzymeDetector offers an automatic comparison, evaluation and prediction of enzyme function annotations for prokaryotic genomes. The biochemical reaction database BKM-react contains non-redundant enzyme-catalysed and spontaneous reactions and was developed to facilitate and accelerate the construction of biochemical models.