Bicuspid aortic valve (BAV) is the most common congenital cardiac defect and prone to premature degeneration causing aortic regurgitation (AR). The assessment of AR in athletic individuals poses several challenges as the pathological left ventricle (LV) remodelling caused by AR may overlap with the physiological remodelling of intense exercise. The purpose of this study is to highlight these challenges, review the existing literature and discuss how to tackle these conundrums. As a real-world example, we compare the resting transthoracic echocardiographic (TTE) findings in a cohort of individuals with BAV and AR, sub-grouped into “highly active” or “lightly active”.Adult male subjects with an index TTE performed at a tertiary referral centre between 2019 and 2022 were included if the TTE confirmed a BAV and at least moderate AR. Further strict inclusion criteria were applied and parameters of valve disease severity was made in accordance with existing guidelines. Subjects completed a physical activity questionnaire over the telephone, and were classified into either group 1: “highly active” or group 2: “lightly active” based on their answers. Demographics and TTE parameters were compared between the two groups.30 male subjects (mean age 44 ± 13 years) with BAV-AR were included – 17 were highly active, and 13 lightly active. There was no significant difference in age , height (p = 0.45), weight (p = 0.268) or severity of AR, when quantitative assessment was possible. Group 1 had a significantly higher stroke volume , larger LV volumes, diastolic dimensions and significantly larger bi-atrial and right ventricular size. This LV dilatation in the context of AR and athleticism poses a diagnostic and management conundrum. Despite this, none of these 17 highly active individuals demonstrated any of the traditional criteria used to consider surgery.There is significant overlap between the physiological adaptations to exercise and those caused by AR. Multi-modality imaging and stress testing can aid clinicians in diagnostic and management decisions in exercising individuals when there is discordance between AR severity and symptoms. Bicuspid aortic valve (BAV) is the most common cardiac defect, with an estimated prevalence of 1–2% in the general population [The assessment of AR in athletic individuals poses several challenges as the pathological left ventricular (LV) remodelling caused by AR may overlap with the physiological remodelling of intense exercise. LV dilatation and low-normal or mildly impaired LV systolic function can be both features of severe AR requiring surgical intervention and athletic adaptation in an endurance athlete . This isThe aim of this study is to describe the transthoracic echocardiogram (TTE) findings in individuals with significant BAV-related AR (BAV-AR) and make comparisons between athletic versus sedentary individuals. By doing so, we aim to to highlight the challenges, review the existing literature and promote discussion on how to overcome these challenges.Adult subjects (> 16 years old) with an index TTE performed at a tertiary referral centre between January 2019 and January 2022 were included if the TTE confirmed a BAV and at least moderate AR. The specific inclusion and exclusion criteria are shown in Table Subjects were consented to complete a telephone questionnaire pertaining to their current and previous exercise levels. Subsequent quantification of each activity into metabolic equivalents (METs) was performed, as outlined by the Compendium of Physical Activities . Subjectt-test. Formal ethical approval was obtained from the Health Research Authority (HRA) in order to complete the exercise questionnaire (REC reference number 22/SC/0358).Statistical analyses were performed using SPSS 2021 edition . Results are mean ± standard deviation (SD) for continuous variables and comparisons between groups made using Student 273 individuals with BAV had their index TTE performed at our institution between January 2019 and January 2022. The majority were male (72% (199/273). From the male cohort, 30 subjects met the inclusion criteria, mean age 44 ± 13 years (range 19 to 62). According to the aforementioned classification, 13 subjects were lightly active (group 1) and 17 subjects highly active (group 2). In group 1, the majority had moderate AR (8/13), 4/13 moderate-severe AR and 1/13 severe AR. In group 2, 10/17 had moderate AR and 7/17 had moderate-severe AR.In the highly active cohort, the vast majority of individuals performed activities with a predominantly high dynamic, low static component . The preThe differences between the two groups are shown in Table Highly active individuals had a significantly lower resting heart rate , higher stroke volume  and significantly larger left ventricular volumes and diastolic dimensions . In ourexercise . FurtherStroke volumes: The average stroke volume (SV) of 118mls in the overall AR cohort is higher than the 70-100mls expected in the normal adult heart. This is a reflection of the increased loading conditions of AR. However, in our cohort, the highly active individuals had a significantly higher SV than their less active counterparts. Though this could be due to the severity of AR not actually being similar in the two groups, it could also be due to the additive effect of high intensity exercise on the LV loading conditions.Ejection fraction: Athletic individuals often have a more efficient ventricle, thereby requiring a lower EF to generate the same cardiac output. In our cohort, there was no difference in EF between the two groups, with an LVEF of 61% in the highly active group, despite their larger LV volumes. This suggests that the AR is possibly causing more of a haemodynamic effect on the LV, with increased contractility to compensate for the larger volume. It is only in the later stages of chronic AR that the LV systolic function begins to impair, and is an indication for surgical intervention [rvention . Once thrvention . One couAR eccentricity: BAV-AR tends to be highly eccentric in nature, sometimes with multiple jets and thus conventional quantitative markers of AR severity are often not applicable to this cohort. One relies on qualitative assessment, for which there may be significant intra-observer variability. As a result, one may look for other markers of severity or alternative imaging modalities.Multi-modality imagingAR may be under-estimated by TTE alone. Particularly for the highly eccentric jets of BAV-related AR, there is an incremental value of using 2D and 3D transoesophageal echocardiography (TOE) for further evaluation . CardiacMany individuals with chronic AR may develop aortic root or ascending aorta dilatation, particularly in those with BAV where aortopathy is common . Though Stress testing Exercise testing, can unmask symptoms, reveal exercise-induced arrythmias and provide an objective assessment of physical fitness and is thus a crucial tool used to provide an individual with exercise recommendations in the presence of significant AR , 17. CarUsing exercise stress echocardiography (ESE) to quantify AR severity however is not recommended, as the shorter diastolic time caused by the ensuing tachycardia, invariably leads to an improvement in the AR severity . This haWhen performed, ESE should therefore focus on specific LV parameters. An absence of contractile reserve (CR) (defined as an > 5% increase in LVEF on exercise) has been shown to be a better predictor of LV decompensation after surgery than resting indices of LV function . More reFollow-upIn some cases the dilemma of moderate or severe AR and its resultant haemodynamic impact on the LV may remain despite comprehensive evaluation. In such individuals, follow-up is crucial as progressive LV dilatation or dysfunction or even subtle reduction of fitness levels detected by CPET, may be suggestive of an earlier need for surgery, even if established criteria are not met . In suchWhat are the solutions?This is a single centre study in a tertiary referral centre for sports cardiology, which is prone to referral bias and may account for the greater number of highly active compared with lightly active individuals. It is limited by a small sample size, with only males included so one can not extrapolate these findings to wider populations. Patients were grouped according to their answers to an exercise questionnaire which has inherent issues with recall bias. Moroever, longitudinal follow-up is not provided to assess longer term outcomes and test the validity of our practice and suggestions. However, the primary aim was to describe findings on an individuals’ index resting TTE.There is significant overlap between the physiological adaptations to exercise and those caused by AR. TTE remains the cornerstone of AR assessment in athletic individuals but it has significant limitations, particularly in BAV-AR which is one of the most common valvular disorders encountered by sports cardiologists. Multi-modality imaging and stress testing can aid clinicians in diagnostic and management decisions in exercising individuals when there is discordance between AR severity and symptoms.


Despite the advances in sequencing technology, massive proteins with known sequences remain functionally unannotated. Biological network alignment (NA), which aims to find the node correspondence between species’ protein–protein interaction (PPI) networks, has been a popular strategy to uncover missing annotations by transferring functional knowledge across species. Traditional NA methods assumed that topologically similar proteins in PPIs are functionally similar. However, it was recently reported that functionally unrelated proteins can be as topologically similar as functionally related pairs, and a new data-driven or supervised NA paradigm has been proposed, which uses protein function data to discern which topological features correspond to functional relatedness.Here, we propose GraNA, a deep learning framework for the supervised NA paradigm for the pairwise NA problem. Employing graph neural networks, GraNA utilizes within-network interactions and across-network anchor links for learning protein representations and predicting functional correspondence between across-species proteins. A major strength of GraNA is its flexibility to integrate multi-faceted non-functional relationship data, such as sequence similarity and ortholog relationships, as anchor links to guide the mapping of functionally related proteins across species. Evaluating GraNA on a benchmark dataset composed of several NA tasks between different pairs of species, we observed that GraNA accurately predicted the functional relatedness of proteins and robustly transferred functional annotations across species, outperforming a number of existing NA methods. When applied to a case study on a humanized yeast network, GraNA also successfully discovered functionally replaceable human–yeast protein pairs that were documented in previous studies.https://github.com/luo-group/GraNA.The code of GraNA is available at  Saccharomyces cerevisiae) has been used as the model organism to map molecular pathways of Parkinson’s disease in humans , with kV as the set of the proteins and kE as the set of physical interactions between proteins; In this article, we focus on pairwise NA of two species’ PPI networks. We are given as input an integrated graph ous work , the funG1, G2, and anchor links E12 as input, GraNA first builds positional and distance embeddings as node features for every node. It then uses a GNN, which performs both within- and across-network message passing through PPI edges and anchor links (orthologs and sequence similarity), to enhance and refine those features into final representations that capture topological and evolutionary similarity relationships. GraNA is trained with protein function data to predict whether a pair of across-network proteins share the same function.We propose, GraNA, a novel framework based on GNNs for supervised NA . ReceiviG1, G2, and anchor links E12, our model can learn an embedding for each node that encodes information of both graph topology and relationships of anchor links. GraNA has L layers of graph convolution blocks, where the i’s embedding GNNs have been widely used to model graph-structured data such as social networks, physical systems, or chemical molecules . Here, wi in terms of the within-network edge set γ is a learnable parameter known as the inverse temperature. Next, node embeddings are updated with across-network message passing through anchor links:where i in terms of the across-network edge set E12, and ω is a learnable temperature parameter. The final updated embedding Within each graph convolution blocks are within- and across-network propagation layers that update the node embeddings. In the nnection : hiℓ+1=fpagation  and one pagation . Pair nopagation  and ReLUpagation  are applAfter the graph convolution, the representations of nodes While GNNs are able to learn node embeddings that encode topological information of the input PPI network structure, previous studies have found that GNNs might perform poorly when the graph exhibit symmetries in local structure, such as node or edge isomorphism. This is related to the theoretic limitation of GNNs due to their equivalence to the 1-Weisfeiler-Lehman test of graph isomorphism . Some exInspired by several solutions in graph machine learning , we intrM in a closed form:where A is the n × n adjacency matrix of the network, D is the diagonal degree matrix, G, b is the parameter for negative sampling, T is the context window size. Unlike the adjacency matrix A that only contains direct neighbor relationships, the NetMF matrix M encodes the similarity between long-distance neighbors. The entry ijM approximates the number of paths with length up to T between nodes i and j. In GraNA, setting b = 1 and T = 10 following the default choices , denoted as e set In , 2021.G1 that are involved in positive pairs, i.e. V1 and V2 are involved in the positive set, for most randomly sampled negative pairs , it is likely that p and q are new proteins that did not occur in p, q) whether We reason that the random negative sampling might lead the machine learning model to learn the node’s presence in the training data rather than functional relatedness. Denote p1, q1) and , we swap their endpoints and add new edges  and  to the negative set if there did not show in To encourage the model to learn the functional relatedness instead of node representativeness in the training data, we propose a hard negative sampling strategy to construct the negative set, where the sampled negative edges must contain nodes that have both appeared in positive edges. We achieve this by performing edge swap between positive edges: given two positive pairs  were downloaded from BioGRID (version 3.5.187) (The PPI network data of six species (3.5.187) . We used3.5.187)  and down3.5.187) . For seq3.5.187)  to perfoous work , and we ous work . The stais a and part of relations, and included evidence codes EXP, IDA, IMP, IGI, and IEP. As GO terms appearing at the higher levels of the GO hierarchy might be too general or redundant, following ETNA  from GO  2020-07, we onlying ETNA  and otheing ETNA , 2021, wing ETNA . The staS. cerevisiae, M. Musculus, C. elegans, and D. melanogaster, and between two yeast species (S. cerevisiae and S. pombe). The prediction task was formulated as a link prediction problem, i.e. predicting whether two proteins have the same function. We created an out-of-distribution train/test split (with a ratio of 8:2) such that proteins present in the training set never occur in the test set. In another more challenging split, we further forced that the training proteins and test proteins do not have We first assessed GraNA’s ability for NA by applying it to align the networks between human and four major model organisms, including We compared GraNA to two unsupervised embedding-based methods , a grapThe evaluation results suggested that GraNA consistently outperformed other methods for aligning functionally related proteins in all five NA tasks in terms of the AUROC and AUPRC metrics . PrecisiIn addition, compared to TARA-TS and TARA++, the only methods for the supervised NA paradigm in literature, we found that our method is a more powerful deep learning solution for supervised NA. For example, GraNA-o on average had 53% higher AUPRC scores than TARA-TS. Interestingly, TARA-TS, despite as a supervised method, sometimes even had a lower performance than the state-of-the-art unsupervised method ETNA. The potential reason is that TARA-TS only used a linear logistic model that only able to model linear feature interactions in the data, while GraNA is an end-to-end GNN, which captures more complex, non-linear feature dependencies, and can better exploit topological similarity and predict node alignment.Moreover, although GraNA-o outperformed other methods in most scenarios, in a few cases, it was only on par with the second-best baseline TARA-TS; .On a more challenging data split where the sequences in the train and test sets have no sequence identity  TARA-TS . We also TARA-TS . This stAdditionally, we created another challenging evaluation dataset based on a temporary split strategy, where the snapshot of the GO database as of 2018-07-02 was used as training data, and the GO snapshot as of 2022-12-04, excluding all training annotations, was used as test data. On this dataset, we again observed similar results where GraNA outperformed baselines such as ETNA and TARA-TS . This deOverall, these results demonstrated that GraNA can better explore topological similarity to accurately align networks. The flexible GNN framework further allowed GraNA to integrate heterogeneous data types that capture multi-view similarity relationships to improve the alignment quality.One important application of NA is to better understand human protein functions by transferring our learned function knowledge about model organisms. Therefore, after evaluating the performance of aligning functionally related proteins, we next studied whether the NAs produced by GraNA can facilitate protein function prediction. Here, we applied GraNA to generate the alignments between humans and the four model organisms. Then, we considered the top 5,000 ranked protein pairs aligned by GraNA and calculate the Jaccard index between the functional annotations of the two proteins in each pair. As a protein may have multiple functions, this evaluation aimed to quantify the overlap between the sets of functions of the two aligned proteins, which was more complex and challenging than the evaluation in the last section which predicted whether two proteins share at least one function. We also compared a random baseline that randomly samples 5000 pairs from proteins that have at least one GO term, in addition to our previously introduced baselines. Furthermore, we have also evaluated GraNA in an established protein function prediction framework .S. cerevisiae). On the alignment task between human (H. sapiens) and roundworm (C. elegans), GraNA achieved performance on par with the second best baseline, which was likely due to that the PPI of C. elegans is the sparsest among all four model organisms  and combining both of them led to the best AUPRC score . InteresAnother novel design in GraNA is the hard negative sampling which prevented the model from only learning from trivial training samples. To better illustrate this, we compared GraNA models trained with three negative sampling strategies, including easy, semi-hard, and hard negative sampling (Methods). We observed that GraNA trained with easy and semi-hard samplings already outperformed the second-best baseline, and using the hard sampling further improved the AUPRC by 20% and showed a more significant margin over baselines . Hard neWe used both distance features (NetMF embeddings) and positional features (Laplacian embeddings) to initialize the node features in GraNA. Here, we analyse the effect of the node features by comparing GraNA variants that used only one or both of the NetMF and Laplacian embeddings, or randomly initialized node features. We observed that with random node features, the prediction performance was only comparable with the unsupervised ETNA method . When reFinally, we demonstrate the applicability of GraNA using a task of identifying replaceable human–yeast gene pairs. Recent studies have identified many human genes that can substitute for their yeast orthologs and sustain yeast growth , which pS. cerevisiae that we used in this work, we obtained 411 gene pairs, out of which 174 replaceable pairs are labeled as positive samples and the remaining as negative. To avoid potential signal leakage, in our data we further removed 169 orthologs that coincide with the 411 pairs. Using this data as a binary classification test set, we first applied a baseline method, ETNA, to predict the replaceability of each human–yeast pair. We observed that ETNA’s predicted performance was nearly random  to predict for those 411 gene pairs. Even though GraNA-pt was not directly trained to predict replaceability, we found that it still had a better-than-random prediction accuracy (AUC = 0.56; We collected the experiment data from PRE8, GraNA correctly predicted a positive z-score for replaceable genes and a negative z-score for non-replaceable genes (AUC = 0.91; As a case study, we applied GraNA to study the replaceability in protein complexes. We selected as two examples the proteasome complex and the CCT complex that have experimental validation data , 2022. IOverall, these results demonstrated the applicability of GraNA for extending the NAs to empower other functional analyses of genes and proteins.NA is a fundamental problem in various domains, such as linking users across social network platforms , unifyinbtad241_Supplementary_DataClick here for additional data file.


Healthcare data and the knowledge gleaned from it play a key role in improving the health of current and future patients. These knowledge sources are regularly represented as ‘linked’ resources based on the Resource Description Framework (RDF). Making resources ‘linkable’ to facilitate their interoperability is especially important in the rare-disease domain, where health resources are scattered and scarce. However, to benefit from using RDF, resources need to be of good quality. Based on existing metrics, we aim to assess the quality of RDF resources related to rare diseases and provide recommendations for their improvement.Sixteen resources of relevance for the rare-disease domain were selected: two schemas, three metadatasets, and eleven ontologies. These resources were tested on six objective metrics regarding resolvability, parsability, and consistency. Any URI that failed the test based on any of the six metrics was recorded as an error. The error count and percentage of each tested resource were recorded. The assessment results were represented in RDF, using the Data Quality Vocabulary schema.For three out of the six metrics, the assessment revealed quality issues. Eleven resources have non-resolvable URIs with proportion to all URIs ranging from 0.1%  in the Anatomical Therapeutic Chemical Classification to 13.7% (17/124) in the WikiPathways Ontology; seven resources have undefined URIs; and two resources have incorrectly used properties of the ‘owl:ObjectProperty’ type. Individual errors were examined to generate suggestions for the development of high-quality RDF resources, including the tested resources.We assessed the resolvability, parsability, and consistency of RDF resources in the rare-disease domain, and determined the extent of these types of errors that potentially affect interoperability. The qualitative investigation on these errors reveals how they can be avoided. All findings serve as valuable input for the development of a guideline for creating high-quality RDF resources, thereby enhancing the interoperability of biomedical resources.The online version contains supplementary material available at 10.1186/s13326-023-00299-3. The acquisition and comprehension of health data and knowledge are crucial for improving the quality of care for patients. Health data enables healthcare providers to obtain a complete picture of a patient’s health status. It is considered to be useful to represent data and knowledge on the web in Resource Description Framework (RDF) to make them Findable, Accessible, Interoperable, and Reusable (FAIR) –5, so thhttp://www.ebi.ac.uk/efo/definition> is used as a predicate of a triple in the Orphanet Rare Disease Ontology (ORDO) resource to provide definitions of its subjects; however, this URI is not resolvable , making it impossible to retrieve the information  of the resource that the URI points to in a machine-readable manner. Without this definition, it is also impossible to automatically determine whether it is a property or a class. It cannot be semantically distinguished from the property ‘iao:definition’ (http://purl.obolibrary.org/obo/IAO_0000115), another property that is also used to provide definitions as described in the Information Artifact Ontology (IAO). As this example demonstrates, the use of non-resolvable URIs can hamper the ability to provide additional semantics, reduce the quality of the resource, and hence should be avoided.This feature enables resource integration in a more meaningful and seamless manner. However, quality issues in the RDF representation of resources can hamper this advantage of RDF data. For example, the URI <http://purl.org/fqm#>, reflect three dimensions: resolvability, parsability, and consistency.A set of six foundational metrics  was propIn the domain of rare diseases, the added value of making health resources linkable and semantically interoperable is more important, compared to the domain of common diseases, where sufficient data is often available for analysis. In Europe, a disease is considered ‘rare’ when its prevalence is less than 5 per 10,000 people . Such raTherefore, we aim to assess the quality of existing RDF resources relevant in the domain of rare diseases, according to the six foundational metrics, and to provide recommendations for the creation of high-quality RDF resources, specifically in the domain of rare diseases.In this section, we describe the process of selecting RDF resources for rare diseases, introduce the metrics used, and describe the workflow for quality assessment and the quality model for structuring the assessment report.https://resourcemap.ejprarediseases.org/.An EJP RD resource map. It exhibits the various resources that make valuable contributions to the rare-disease domain and collaborate with the EJP RD: A list of FAIR implementations. Data stewards in the EJP RD , 12 use We searched for existing rare-disease resources through:From these resources, we selected those for which an RDF representation exists.All the experiments mentioned in this paper were conducted on a MacBook Pro with a 2.3 GHz 8-Core Intel Core i9 processor and 16 GB 2400 MHz DDR4 memory.We used the six metrics to assess the quality of RDF resources on rare diseases, see their definition in Table The components of RDF resources, namely URIs, literals, and Blank nodes , are extThe HTTP status codes for URIs are retrieved, and URIs with the status code as ‘4xx client error’ or ‘5xx server error’ are classified as non-resolvable (the ‘non-resolvable URIs’ metric).The content-types of resolvable URIs are retrieved and used to categorize them as URIs that have or do not have content-type RDF. RDF content-type is the Media Type  that corFor every parsable URI its specification is extracted from the parsed graph. If no such specification exists, the URI is classified as an undefined URI.The types of all defined URIs are extracted to identify ‘classes’  and ‘properties’ (those of ‘rdf:Property’ or any OWL property).The deprecation of each class and property is examined. A class C is deprecated if one of these triples exists: The role of classes in the triples is assessed. A class is misplaced, if it is used as the predicate of a subject-predicate-object triple. (the ‘misplaced classes or properties’ metric).The role of properties in the triples is assessed. A property is misplaced, if it is used as the object of a subject-predicate-object triple. There is an exception in which a property may be the object of defining triples whose property is used to define terms, such as ‘rdf:type’ and ‘rdfs:subPropertyOf’ (the ‘misplaced classes or properties’ metric).The properties with a correct role in the triples are investigated whether they are ‘owl:dataTypeProperty’ or ‘owl:ObjectProperty’. The ‘owl:dataTypeProperty’ is misused if the related object is a URI; The ‘owl:ObjectProperty’ is misused if the related object is a literal (the ‘misuse of owl:dataTypeProperty or owl:ObjectProperty’ metric).An assessment report is generated, which contains all the assessment results: a list of all errors  and their proportions to all unique URIs. The number of triples affected and their percentage is calculated for quantitative analysis.The workflow of quality assessment consists of the following steps aligned with , comprisThe quality assessment of RDF resources following the workflow on the aforementioned metrics  . Figure Which rare-disease resources have more than 10% non-resolvable URIs?Which rare-disease resources have undefined URIs? Which are these undefined URIs?What quality issues are identified in the WikiPathways WP Ontology? Which metrics are they referring to? What is the definition of these metrics?To demonstrate the benefits of utilizing this semantic representation for assessment reports, we formulated three questions to be answered through SPARQL querying : Which rThis demonstration process was implemented in Ontotext GraphDB , an RDF Sixteen rare-disease resources were selected, as shown in Table After assessing these resources, the test revealed quality issues on three metrics: ‘non-resolvable URIs’, ‘undefined URIs’, and ‘misused owl:ObjectProperty or owl:dataTypeProperty’, as shown in Table http://www.w3.org/2004/02/skos/core#definition>), OWL [http://www.w3.org/2002/07/owl#versionIRI>), and RDFS [http://www.w3.org/2000/01/rdf-schema#label>).Except for four resources that have no non-resolvable URIs  and SNOMED CT, which is a special case, as is addressed in the Discussion, the proportion of non-resolvable URIs in the remaining eleven resources ranges from 0.1%  in ATC to 13.7% (17/124) in the WikiPathways Ontology. These non-resolvable URIs have affected multiple triples within the resources, ranging from 0.5%  in GO to 58.4% (87/149) in the WikiPathways Ontology. Ninety-nine percent of URIs from SNOMED CT are non-resolvable and they all are the terms defined by SNOMED CT. The remaining 1% resolvable URIs are the terms from SKOS , hPSCreg vocabulary (1), Resource Metadata Ontology (2), the WikiPathways Ontology (1), the UniProt ontology (2), HPO 60), and GO (2), see Table 0, and GOhttp://purl.obolibrary.org/obo/MI_0915’ (with quotes) is recognized as ‘string’ by computers and therefore of incorrect type, whereas <http://purl.obolibrary.org/obo/MI_0915> is recognized as a URI. In this instance, the object, not the property, causes the inconsistency.Only WikiPathways Ontology and HPO have shown inconsistency between the owl:ObjectProperty property and the linking object that should be a URI  rather than a literal . The triples including these properties are shown in Table Conforming to the DQV quality model, sixteen assessment reports in Turtle serialization format were generated upon the completion of the rare-disease resources assessment procedure. Figure As depicted in Fig. Which rare-disease resources have more than 10% non-resolvable URIs? Five resources contain over 10% non-resolvable URIs. This is answered by first querying the quality measurements that are based on the ‘fqm:uriNonResolvableMetric’, and then filtering the recorded value according to the ‘dqv:value’ property.Which rare-disease resources have undefined URIs? Which are these undefined URIs? There are 69 undefined URIs with corresponding resources listed in the query results. This is answered by first querying the quality measurements based on the ‘fqm:uriUndefinedMetric’, and then retrieving all the URIs following the ‘dcterms:relation’ property.What quality issues are identified in the WikiPathways WP Ontology? Which metrics are they referring to? What is the definition of these metrics? There are three types of quality issues identified. In the query results, their corresponding metrics with definitions are displayed. This is answered by querying for existing quality measurements with their metrics, and then retrieving the definitions following the ‘skos:definition’ property which is used in the FQM ontology.In this paper, we applied six metrics to assess the quality characteristics of RDF resources in the rare-disease domain. We found a few issues when assessing the quality of these resources: eleven out of sixteen resources have non-resolvable URIs; seven resources have undefined URIs; two resources have inconsistency related to the ‘owl:ObjectProperty’ properties. Individual findings will be discussed in more depth in the sections that follow.https://creativecommons.org/licenses/permits> and the class <http://web.resource.org/cc/Attribution> to describe the Creative Commons licenses. However, both of these are non-resolvable. The correct ones are <https://creativecommons.org/ns#permits> and <https://creativecommons.org/ns#Attribution> [Numerous resources such as the ORDO used the property <ibution> . This imhttp://www.w3.org/ns/prov-o> in the EJP RD Resource Metadata Ontology . These examples show that any approach or technique based on pattern matching is heavily reliant on the accuracy of URIs. Also classified as ‘undefined’ are the other two ontology URIs <http://www.w3.org/ns/dcat#catalog>) is a property while ‘dcat:Catalog”  is a class. Their ‘path’ parts, ‘#catalog’ (lowercase) versus ‘#Catalog’ (upper case), are different. Such a small distinction makes it easy to confuse them. However, this issue can be alleviated by incorporating codes into the naming, for example, the ‘is located in’ property <http://semanticscience.org/resource/SIO_000061> and the class ‘female’ <http://purl.bioontology.org/ontology/SNOMEDCT/248152002> using only numbers.Besides, URIs whose ‘path’ part contains letters are more susceptible to any operation that is affected by case sensitivity. For example, ‘dcat:catalog’  used in the hPSCreg vocabulary. This term does not exist; however, ‘rdfs:Resource’ does. This is probably due to the misinterpretation of existing terms. Both examples demonstrate the need for automated quality assessment by machines to detect errors that are often hard to detect by humans.Mismatched prefixes or terms are a common cause of undefined URIs. One example is <mespaces  were mixhttps://www.ietf.org/rfc/rfc3986.txt> with the ‘text/plain’ content-type in the ‘rare-disease biobank and registries’ resource and the URI <https://github.com/geneontology/go-ontology/issues/7549> with the ‘text/html’ content-type in HPO properly use non-RDF content. It is also essential to emphasize that the purpose of identifying errors in these resources is not to dissuade people from using them, but rather to suggest areas for improvement so that the rare-disease community can benefit from ‘linked data’ and RDF.Importantly, we do not regard a URI that does not have content-type RDF to be an error because such a URI already indicates that it does not provide an RDF representation. For instance, the URI <Our effort to assess the quality of RDF resources in the domain of rare diseases has several strengths. First of all, a significant strength is that the metrics applied are objective and automatable, allowing the quality assessment to be easily scalable when applied to other RDF resources while yielding reliable results. Secondly, the assessment report is generated in the form of RDF, allowing the quality information to be shared and reused in the future to accommodate the dynamic nature of resources in the world of Linked Data.http://purl.obolibrary.org/obo/IAO_0000120> which stands for ‘metadata complete’ and is an instance of ‘curation status specification’ , i.e., defined as ‘owl:NamedIndividual’ rather than ‘owl:Class’ or ‘rdfs:Class’. Only the metrics regarding resolvability and parsability are applicable, so the tool only tested instances based on these two metrics. Nevertheless, it is necessary to include additional metrics that measure different aspects of instances, which should be the subject of future work. One example of a metric may be detecting an instance as a type of two disjoint classes, which can lead to inconsistency.There are limitations in the implementation of the assessment of the metrics. First, the current evaluation tool relies on pattern matching and is limited to the syntactical level, therefore does not deem two URIs with and without hashtags as identical. Second, the current version of the tool does not adequately handle instances. One example is the URI <http://snomed.info/’) return the status code 423 Locked. This is not a quality issue of these URIs but is attributed to a blocking mechanism, despite retry and sleep functions being applied in the software. Both functions again increase the total running time of implementation. To enable consistency assessment in this type of cases, one potential approach is to retrieve a complete RDF representation of the resource, such as an ontology, a schema, or a (meta)dataset, and make it available in a triplestore as a temporary RDF graph to be referred to by assessed URIs.Given the size of biomedical ontologies, it is necessary to design the most computationally efficient methods prior to metric implementation in terms of memory consumption and time cost, especially for a large-sized ontology  or when an ontology server has a blocking mechanism to prevent repeated external requests. For example, the assessment of SNOMED CT revealed that all the URIs stemming from SNOMED CT  each serialization format as an individual resource and link the quality measures to the particular format assessed. Through the property ‘dcat:distribution’, each (resource in) serialization format can be linked to the original resource URI, such as DCAT <https://www.w3.org/ns/dcat#>.Even though the current quality model is adequate for representing the quality metadata in RDF, the more resources are investigated, the more amendments or extensions may be required. DCAT <Non-resolvable URIs: (1) If one creates URIs, ensure that they are resolvable. Non-resolvable URIs need to be corrected and all URIs need to be tested periodically. (2) Avoid using URIs from external resources that are non-resolvable. Even if within a commonly-used ontology such as the ORDO, there are 42 non-resolvable URIs, which are used to describe rare-disease conditions.Undefined URIs: (1) If one creates URIs, it is recommended to only include digits in their naming so that they are case insensitive [ensitive . (2) If Inconsistent URIs: (1) If one creates classes or properties, ensure that they adhere to intrinsic characteristics as ‘owl:Class’ or ‘rdfs:Property’, ‘owl:ObjectProperty’ or ‘owl:DataTypeProperty’; (2) If one reuses existing classes or properties, ensure that they adhere to the same intrinsic characteristics and that they are not deprecated.In this paper, we consider a resource to be of high quality if it does not have any foundational quality issues. Although some , 24 arguThere are some studies that investigated the quality issues related to foundational quality. Johannes et al. , 27 highGiven the objective and automatable nature of the foundational quality metrics, it will be necessary in the future to assess resources in other domains to identify more quality issues in the real world, and accordingly to develop domain-specific guidelines.We assess the resolvability, parsability, and consistency of RDF resources in the rare-disease domain, and identify various types of errors. Using non-resolvable URIs is the primary quality issue, and there are numerous causes for undefined URIs. Based on the findings, recommendations regarding URIs have been provided. In the future, it will be necessary to incorporate more real-world scenarios to enable the assessment of resources from more diverse sources. Potentially, the applied methods for quality assessment can be integrated into the process of generating RDF resources, thereby enabling real-time quality assurance as opposed to post-hoc assessment and curation.Additional file 1. The SPARQL query with the result to answer the third proposed question.


As advanced age affects body organs and systems, older people are more vulnerable to neurological conditions or disorders. This Research Topic has collected articles that provide opinions and perspectives related to the field of neural rehabilitation for the elderly, particularly on aspects such as neuromotor function, rehabilitation, and exercise.Tao et al. discussed cognitive-motor dual task training (CMDT) for the prevention and treatment of aging-related cognitive impairment. Compared to a single training modality, CMDT appears to be a more effective intervention for improving cognitive function and brain structure, due to its synergistic and complementary nature. Therefore, CMDT offers a promising intervention strategy for aging-related cognitive impairment. Although it has a good prospective application, the standardization of its applications and the underlying neurophysiological mechanisms require further investigation.With aging, older adults experience significant declines in cognitive function. Li et al. discussed the role of exercise in healthcare, particularly the importance of exercise in the prevention and treatment of a range of age-associated diseases or health conditions. Several modules and principles for implementing exercise as a form of medicine were proposed, with considerations of appropriate intensity and potential side effects. Given that the lack of exercise is a global health concern, “Exercise is Medicine” is a timely call to promote the involvement of people in health or exercise programs, including the elderly and individuals who experience a disability.In line with the “Exercise is Medicine” initiative advocated by the American College of Sports Medicine and the American Medical Association, Gong et al. discussed the significance of combining electrical impedance myography (EIM) with other commonly used quantitative methods, such as medical imaging, electromyography (EMG), and myotonometry, etc., to assess muscle alterations after stroke. Different combinations were suggested to evaluate morphological and functional changes in paretic muscle. Multimodal parameters resulting from different techniques can facilitate a comprehensive muscle evaluation, which is important for understanding the physiological mechanisms underlying dysfunction and rehabilitation.Quantitative physiological measurements are needed for successful rehabilitation. Zhou et al. presented their opinions on automated theranostics, focusing on technical automation in neuro-behavioral measurements, rehabilitation treatments, and coordination of healthcare resources. Recent progress, existing gaps, and future directions were discussed in depth. In addition, other relevant factors such as cross-disciplinary education and equity for underdeveloped areas were also considered to promote the application of automatic theranostics. These multifaceted advances collectively help implement rehabilitation theories and clinical expertise into automation infrastructures, thus facilitating long-term neurorehabilitation.With the goal of long-term neurorehabilitation after stroke, Hu et al. discussed aging-related changes in speech production, which is a complex neuromotor behavior involving multiple body systems. While the majority of previous studies in this field have mainly examined the acoustic changes, the opinion article focused on the neuromotor control of speech production with aging, which has not been extensively studied. Multiple factors involved in the aging-related neuromotor control of speech production were discussed, including laryngeal physiology, brain structure and function, higher-order cognitive functions, and sex-aging interactions. Understanding the effects of aging on neuromotor control of speech production is important for the appropriate treatment of motor speech disorders that frequently occur with advanced aging.Salvalaggio et al. presented a protocol study designed to investigate the effect of rehabilitation treatment in a group of stroke survivors. Cross-modality protocols were proposed to develop a multidimensional predictive model of sensorimotor recovery related to stroke upper limb rehabilitation, characterized by integrating physiological and imaging techniques with clinical and cognitive assessment, rehabilitation dose and biological variables in stroke patients undergoing a period of intensive rehabilitation. The described study will generate a rich multi-modal dataset in stroke patients. The prospective protocols, if validated, can help promote individualized rehabilitation targeting the best possible outcome.Finally, We hope that this Research Topic will help to promote thoughts and perspectives on recent technological advances, latest discoveries, current challenges, and future directions specifically in the field of neural rehabilitation for the elderly.PZ: Writing—original draft. YZ: Writing—review and editing. SL: Writing—review and editing.


Polycarbonate (PC) with high transmittance, stable mechanical performance and environmental resistance is crucial for practical applications. In this work, we report a method for the preparation of a robust antireflective (AR) coating by a simple dip-coating process of a mixed ethanol suspension consisting of tetraethoxysilane (TEOS) base-catalyzed silica nanoparticles (SNs) and acid-catalyzed silica sol (ACSS). ACSS greatly improved the adhesion and durability of the coating, and the AR coating exhibited high transmittance and mechanical stability. Water and hexamethyldisilazane (HMDS) vapor treatment were further employed to improve the hydrophobicity of the AR coating. The as-prepared coating exhibited excellent antireflective properties, with an average transmittance of 96.06% in the wavelength range of 400 to 1000 nm, which is 7.55% higher than the bare PC substrate. After sand and water droplet impact tests, the AR coating still maintained enhanced transmittance and hydrophobicity. Our method shows a potential application for the preparation of hydrophobic AR coatings on a PC substrate. It can be observed that there is a strong absorption peak at 1074 cm−1 that corresponds to the stretching mode of Si-O-Si bonds [−1 corresponds to the hydroxyl group of Si-OH, and the intensity of this band was significantly weakened by HMDS vapor modification [−1 were discovered by contrasting pure silica with water and HMDS vapor-modified silica coatings. These bands were attributed to Si-C stretching vibration and Si-CH3 symmetric deformation, indicating the presence of -CH3 groups in the modified coatings [3 groups in HMDS.The structure and chemical composition of the coatings have a significant impact on their performance. The hydrophobicity of the AR coating that was treated with water and HMDS vapor increased significantly, which was attributed to the substitution reaction of non-polar hydrophobic methyl groups to replace the polar hydroxyl groups on the coating, resulting in a significant reduction in the surface energy of the SNs@ACSS coating. FTIR spectroscopy revealed several characteristic absorption bands between pure silica as well as water and HMDS vapor-modified silica, as shown in Si bonds . The absfication . New abscoatings . These fThe surface of transparent substrates is susceptible to contamination, resulting in a significant loss of transmittance . Being aThe stability of the nanocoatings in practical applications is determined by the mechanical robustness of the AR coatings. Due to the insufficient adherence between nanocoatings and substrates, AR coatings tend to lose their antireflective and hydrophobic properties when exposed to invasive contact. It has been demonstrated that linear silicate-like polymers made from acid-catalyzed silica sols serve as an inorganic binder ,42. In tIn this study, the mechanical stability of the as-prepared hydrophobic AR coating was evaluated by the sand abrasion test as well as the water droplet impact test. The tape adhesion test was used to assess the adhesion of the antireflective hydrophobic coating . Figure The environmental resistance of AR coatings is crucial for the practical application of nanocoatings ,45. The In this work, the brine corrosion test was also used to evaluate the stability of the coating in a salt solution . Figure In summary, we developed a facile method to prepare an AR coating on PC substrates with high transmittance and enhanced mechanical robustness by mixed SNs and ACSS. Excellent antireflective performance with an average transmittance of 96.06% was achieved in the wavelength range of 400 to 1000 nm. SNs provided high transmittance for the coating, and ACSS was utilized, not only as a binder to enhance the adhesion between the PC substrate and the coating but also to significantly improve the mechanical stability of the AR coatings. Meanwhile, water and HMDS vapor treatment significantly increased the hydrophobicity and environmental resistance of the SNs@ACSS coating, and the WCA reached 121.5°. After a series of rigorous tests, the as-prepared AR coating maintained its enhanced transmittance and hydrophobicity. This facile method of preparing high transmittance, mechanically stable and environmentally resistant coatings can be applied to a variety of substrates for different applications, such as optical lenses, shatterproof glass and other optical devices.


In this paper, we show that fairness can evolve in the divide-a-lottery game which is more general than the divide-a-dollar game by using an indirect evolutionary approach. In the divide-a-lottery game, the size of a pie is uncertain. Two players sequentially bid for a share and they get their bid if the allocation based on the bids turns out to be feasible and otherwise neither gets anything. In this game, rational players over-compete for a higher share, resulting in a high probability of failure in agreement, whereas fair players who dislike the disparity between shares lower their bids thereby reducing the failure probability and thus increasing the expected payoff. As a result, fairness strictly dominates rationality. This is the mechanism through which fairness evolves. However, this result is not robust against even a slight uncertainty about the opponent’s type. Surprisingly, we show a contrasted simulation result that only rational players who are strictly dominated by fair players survive evolutionarily for most of the parameter values if players have even a slight chance of not knowing the opponent’s type. Our simulation results in a local interaction model in which players only know the type of closer neighbors capture both insights and demonstrate that moderate proportions of both types coexist evolutionarily over time, and that the population average fitness of this polymorphic population is higher than monomorphic population consisting only of fair types or rational types. Considering that the selfish behavior, by definition, maximizes the individual’s utility or fitness and thus only homo economicus appears to be able to survive in the long run, it is rather puzzling that fair behavior survives in the long run in an evolutionary environment. The evidence of fairness is, however, well documented. For example, in the ultimatum game, a robust result across hundreds of experiments is that the vast majority of the offers are between 40 and 50 percent of the available surplus .Although most economists and game theorists assume that material self-interest is the sole motivation of people, there is overwhelming counter-evidence gathered by psychologists and experimental economists. This evidence indicates that a substantial percentage of human beings are strongly motivated by other-regarding preferences including fairness, altruism etc. . A divide-a-dollar game, which is also known as a Nash demand game10 is one of the most widely used bargaining games, describing a procedure of how to split a dollar. Unlike the ultimatum game that is sequential in the sense that one player proposes a share and then the other player decides whether to accept or reject it, a divide-a-dollar game is simultaneous. The game goes as follows. Player 1 and player 2 simultaneously bid the amount of x and y respectively to divide a dollar. If the bids turn out to be a feasible division in the sense that In this paper, we show that fairness can evolve in the divide-a-lottery game which is more general than the divide-a-dollar game by using an indirect evolutionary approach. .In real situations, bargaining is usually proceeded sequentially and both players have a chance to bid. Therefore, we consider a combination of the two bargaining games in which the two players offer bids sequentially. Unlike the ultimatum game, however, the value of the pie is uncertain. We call this a divide-a-lottery game. So, in a divide-a-lottery game, players bargain for a lottery by bidding sequentially.  nor spatial structure of interaction.R) and fair players (F). At any time, they are pairwise matched and play a divide-a-lottery game. The value of a lottery, denoted by v, is uncertain. We assume that it is uniformly distributed on . The divide-a-lottery game goes as follows. First, one player (player 1) of the matched pair bids x and then the other player (player 2) bids y. After that, the value of v is realized. If it turns out that x and y respectively and if 16 and Li et al.17.We consider a population consisting of a continuum of players of finite measure. Players are classified into two types: rational players  is a difference between the shares of the two players.  and the other case in which each player is not informed of the opponent’s type (incomplete information case).We consider two symmetric matching cases, rational player vs. rational player and fair player vs. fair player, and one asymmetric matching case, rational player vs. fair player.x, player 2 seeks to maximize his material payoff by choosingx:x to maximizeSince a stage game is sequential, we use backward induction to obtain the subgame perfect equilibrium. If rational player 1 plays against rational player 2, given the bid of player 1, Let x as given:x to maximizeIf a fair player plays against another fair player, player 2 chooses his bid to maximize his subjective utility, taking his opponent’s bid Let x to maximizeIf player 1 is rational and player 2 is fair, we know from  that \doOn the other hand, if player 1 is fair and player 2 is rational, equilibrium bids are Let mentclass2pt{minimIf the fitness of a player is determined by his material payoff, we can see from Table mentclass2pt{minimProposition 1 Only fair players can survive evolutionarily if a randomly matched pair in a population plays a divide-a-lottery game and the players know each other’s type.21 which is a long-run asymptotic attractor. In this game,  is a strict Nash equilibrium.The analytic proof is omitted, because it is well known that a strict Nash equilibrium is an evolutionarily stable strategy (ESS) by Maynard Smith and PriceC) is strictly dominated by defection (D), but  yields higher fitness than . In other words,  is the collectively rational outcome , whereas  is the individually rational outcome . The discrepancy is where social dilemma comes from. In our divide-a-lottery game, fairness strictly dominates rational behavior, but unlike the PD game, the individually rational outcome  yields higher fitness than . This is the main difference from the PD game. Also, it is interesting to note that the collectively rational outcome in this game is  and , not , for most parameter values except for very small values of At this moment, it is worthwhile to compare this game with the prisoners’ dilemma (PD) game. In a PD game, cooperation  bids very high to the rational opponent, so rational player 2 is severely exploited, while he bids lower to the fair opponent, because he knows that the fair opponent (fair player 2) will bid so high that his high bid would be very likely to lead to a failure in bargaining. However, if players have incomplete information about the opponent’s type, a rational player who is unsure of the opponent’s type must bid lower than when he faces a rational opponent, and so a rational player 2 is not very much exploited. This is one of the main reasons why rational players fare better under incomplete information. Similarly, a fair player who is unsure of the opponent’s type can bid higher if there is a high probability that the opponent is a rational type. So, incomplete information can have the role of making a rational player play more like a fair player and making a fair player play more like a rational player. .Under complete information, a rational player earns a low material payoff because he is significantly exploited when he is the second mover. On the other hand, under incomplete information, he is not so much exploited because the opponent is not sure whether he is rational or not. However, if the proportion of fair players is very high, it becomes an almost complete information game, and the advantage of fairness in the case of complete information is almost balanced with the advantage of rationality in the case of incomplete information, so both of the two types can survive and evolve over time.22 and Hauert and Doebeli23. Initially, there are R or F) is assigned randomly according to the pre-assigned ratio of fair players  and for the pie the value of which is uncertain, we believe that this result gives a sensible prediction in the real world.Supplementary Figure S1.


Rehabilitation improves functional recovery in subarachnoid hemorrhage (SAH) patients, and assessing patients for rehabilitation is the first step in this process. However, little is known about clinical practice in China regarding the assessment and provision of rehabilitation for patients with SAH.To identify patients hospitalized with SAH and to analyze rehabilitation assessment rates, we used data for 11,234 SAH patients admitted to 861 hospitals from the China Stroke Center Alliance from August 2015 to July 2019. We examined factors for rehabilitation assessment and analyzed the relationship between rehabilitation assessment and outcomes in these patients.Among 11,234 patients with SAH, 6,513 (58.0%) were assessed for rehabilitation. Assessed patients had an increased length of stay , a higher Glasgow Coma Scale (GCS) score on admission , and were more likely to be admitted to the stroke unit . In multivariable analysis, factors associated with an increased likelihood of a rehabilitation assessment (p < 0.05) included a longer length of stay , 1.04 to 1.05) and care such as dysphagia screening , DVT prophylaxis  and vessel evaluation . For the multivariate analysis of outcomes, patients undergoing rehabilitation assessment had a longer length of stay , a higher modified Rankin Scale (mRS) score at discharge , and higher rates of discharge to a rehabilitation center .More than two-fifths of SAH patients were not assessed for rehabilitation. Rates vary considerably among hospital grades, and there is a need to improve adherence to recommended care for SAH patients. Stroke is a leading cause of death and disability globally, and stroke rehabilitation improves functional recovery in these patients . ApproxiEarly rehabilitation has been established as an integral part of treatment for SAH care, resulting in reduced mortality, fewer complications and better functional outcomes –7. ThereWe used data from the China Stroke Center Alliance (CSCA). The purpose of the study was to clarify the status of the rehabilitation rate and to evaluate patients with SAH to provide evidence for clinical rehabilitation care.The CSCA program is designed to establish a continuous national stroke registry and help health care providers develop stroke centers and treat patients in a consistent manner in accordance with accepted national guidelines and, ultimately, improve patient outcomes. The CSCA was designed from the CSA under the guidance of the National Center of Neurological Diseases Care Management. The CSCA is a national, hospital-based, multicenter, voluntary, multifaceted intervention and continuous quality improvement initiative. This program is available to all Chinese secondary and tertiary grade hospitals. Hospitals continued to join the program in a staggered manner. Hospital characteristics, including geographic region, teaching status, volume (secondary and tertiary grade) and annual stroke volume, were surveyed. Hospitals intending to join this program contacted the staff of CSCA voluntarily; hospitals were also recruited directly through work with the National and/or Provincial Center of Neurological Diseases Care Management. The number of hospitals from each province was obtained from the 2016 Statistical Yearbook published by the National Health and Family Planning Commission of the People’s Republic of China .Data were collected via a web-based patient data collection and management tool , abstracted via chart review, coded, deidentified and transmitted in a secure manner to maintain patient confidentiality compliant with national privacy standards. The following data were collected for each hospitalized patient: demographics, history of disease and medication, hospital presentation, initial neurological status, medications and interventions, reperfusion strategy and in-hospital outcomes and complications. This patient data collection and management tool has two main functions. The first function is to collect concurrent data. The required items were structured such that valid data must be entered before the data can be saved as a complete record and submitted to the database. The second function of the tool is to analyse and provide data feedback. All hospitals using it received an independent account and password to view the benchmark for adherence to evidence-based performance measures and to compare their own hospital’s current performance to past levels as well as the concurrent standards of other regional hospitals within their purview. Information on stroke care quality was also sent to hospital personnel via the WeChat app, a communication tool for data collection and management .Assessing patients with SAH for the need for rehabilitation is an evidence-based clinical guideline and considered a core component of rehabilitation care , 15. As The proportion of patients who received assessment for rehabilitation is described at the patient level. The adherence rate of rehabilitation assessment at the hospital level was defined as the total number of eligible patients receiving rehabilitation assessment divided by the total number of eligible patients at each hospital. Continuous variables are described as the mean ± standard deviation or median [25th-75th percentiles]. Categorical variables are presented as absolute numbers with percentages. Due to the large sample size, differences that were statistically significant may not be clinically meaningful. We used absolute standardized differences (ASDs) to compare the differences in patients’ baseline characteristics because unlike the t test, χ2 test, and other statistical tests, the ASD method is not dependent on sample size; an ASD > 10 indicated significant differences between groups . MultivaSince the main purpose of the CSCA is to facilitate quality improvement, at the local level, data collection by the site is seen as a quality improvement tool. The participating hospitals are authorized to conduct quality of care assessments and have research approval to collect data from CSCA without the need for individual patient informed consent under common rules or authorization and exemption from institutional review boards. Indeed, informed consent may lead to sampling bias, which may compromise the validity and generalizability of the database. Patient confidentiality is protected in the following ways: (1) data are removed from all identifiers before their use in research, and (2) the use of data for these purposes is closely supervised by the China National Clinical Research Center for Neurological Diseases (NCRCND) analytic center .Patients who met the following criteria were recruited consecutively at all 1476 hospitals from August 2015 to July 2019: (1) aged 18 years or older; (2) a primary diagnosis of SAH confirmed by brain CT or MRI; (3) symptom onset within the last 7 days; and (4) admitted either directly to wards or through the emergency department. Patients with ischemic stroke, TIA, cerebral hemorrhage, cerebral venous sinus thrombosis, or non-cerebrovascular disease and patients referred to two or more hospitals within 7 days were excluded.N = 7, 0.06%). The final study sample was 11,234 SAH patients from 861 hospitals  were diagnosed with SAH on admission and eligible for this study. Patients without complete rehabilitation assessment information were excluded (The median rate of rehabilitation assessment was 55.56% (interquartile range [IQR] 16.67–100%) and varied significantly among the 861 participating hospitals, with 0% for 189 and 100% for 226  underwent an assessment for rehabilitation  and care such as dysphagia screening , DVT prophylaxis  and vessel evaluation . In contrast, hospitalization in the ICU , being an inpatient at a central hospital , and treatment at a lower-grade hospital  were associated with a lower likelihood of a rehabilitation assessment , were more likely to have an adverse prognosis (27.9% versus 21.0%), were less likely to experience in-hospital mortality (1.5% versus 5.2%), and were more likely to be discharged home (77.1% versus 62.0%)  , a higher modified Rankin Scale (mRS) at discharge , lower in-hospital mortality , higher rates of discharge to home  and higher rates of discharge to a rehabilitation center   is considered the most effective site of treatment for stroke , comprisThe median hospital length of stay of SAH patients in our study was 14 days, and the longer the hospital stay was, the more likely a patient was to receive rehabilitation assessment. This finding is similar to the report of the Get With The Guidelines program in America that a shorter length of stay is associated with a lower chance of receiving an assessment for rehabilitation . In bothThe quality of medical care is receiving increasing attention worldwide . We founCompared with secondary hospitals, tertiary hospitals have rich medical resources and treat patients with complicated conditions. Overall, the medical personnel at these facilities carry out more comprehensive treatment and intervention, pay more attention to the prognosis of SAH patients and are more likely to perform rehabilitation assessments. Although higher grade hospitals are more likely to assess SAH patients for rehabilitation, a greater number of stroke discharges annually decrease the likelihood of assessment. The total amount of medical resources per capita is low in China compared with most developed countries . For exaCompared with patients who did not undergo rehabilitation assessment, those with rehabilitation assessment had a longer length of stay, higher levels of disability (mRS scores) at discharge, lower in-hospital mortality, were more likely to be discharged to home and were more likely to be discharged to a rehabilitation center. Some general hospitals contain independent rehabilitation wards, and SAH patients who have undergone rehabilitation assessment can be rehabilitated in their own hospital if they need rehabilitation training without transfer, thus increasing the length of stay. In contrast, some lower-level hospitals do not have rehabilitation facilities, and therefore patients need to be transferred to rehabilitation centers for further rehabilitation training after rehabilitation assessment. Patients who return home are divided into two categories: those with mild illness, no residual disability, and no rehabilitation training; and those with a particularly severe condition, near death, and with no need for rehabilitation.The limitations of this study included the following. First, hospital registry participation was voluntary, and participating hospitals were more likely to focus on improvements in stroke care quality. These hospitals may represent a higher standard of stroke care than is available nationwide. Second, a high rate of missing data for the GCS score limited our ability to adjust for confounding by SAH severity. Third, this study did not exclude patients who were unsuitable for physical therapy, such as patients who died within 1–3 days after a stroke or those who were transferred from a lower-grade hospital to a higher-grade hospital. Fourth, conditions may have influenced outcomes, such as lower rates of poor outcomes and in-hospital mortality among patients undergoing rehabilitation assessments. In addition, limitations of this study include not taking into consideration the clustering effect of the hospitals, and the study design was a cross-sectional study without randomization. Despite these limitations, our study provides a comprehensive characterization of rehabilitation assessments for a large cohort of SAH patients.In summary, a documented assessment for rehabilitation was not found for two-fifths of patients with SAH, which was associated with a greater than threefold increase in mortality. Analysis of SAH patients treated at hospitals in CSCA identified that the rate of rehabilitation assessment should be improved. Establishing standards for rehabilitation in care may require local customization with additional training, consultation and multidisciplinary teamwork to match the resources available. Studies on the effects of rehabilitation in different models of SAH in China can support improvements in evidence-based recommendations for care.


In the present study, sympathetic skin response (SSR) characteristics were explored in children with Guillain–Barré syndrome (GBS) and the value of early diagnosis and prognostic evaluation in GBS complicated by autonomic dysfunction (AD) was evaluated.A total of 25 children with GBS and 30 healthy controls (HCs) were enrolled in this prospective study. SSR findings for the two groups were compared. SSR and nerve conduction study (NCS) results were compared among patients with GBS, and differences in clinical characteristics between the groups with abnormal and normal SSR were analyzed.P < 0.05). There was no statistically significant difference between SSR and NCS results in the acute phase of GBS (P > 0.05), and there was no significant difference in the rate of AD or in Hughes functional grade at nadir between the groups with abnormal and normal SSR (P>0.05). However, there was a statistically significant difference between the results of SSR and NCS tests during the recovery phase (P = 0.003). Abnormal SSR mainly occurred in cases of the acute inflammatory demyelinating polyradiculoneuropathy (AIDP) subtype. In addition, SSR was abnormal in all pediatric GBS patients with poor prognosis 1 month after onset of symptoms.Within the GBS group, six patients (24%) required mechanical ventilation, 17 patients (66.7%) had AD, 18 patients (72%) had an abnormal SSR, and 13 patients (52%) had AD combined with SSR abnormalities. There was a statistically significant difference in SSR latency in the lower limbs between the GBS group and HCs (Two-thirds of the children with GBS have AD. SSR could be used for early diagnosis and follow-up of GBS and may also be helpful in evaluating disease severity and short-term prognosis. Guillain–Barré syndrome (GBS) is the most common cause of acute flaccid paralysis in children . The incTwo-thirds of patients with GBS have autonomic dysfunction (AD) , such asWe prospectively recruited GBS patients who were admitted to our neurology department between 2018 and 2022. Inclusion criteria for the GBS group were as follows: (I) patients aged ≥4 years and ≤16 years; (II) those who met level 2 of the Brighton criteria for GBS , 12; andThe following clinical characteristics were evaluated: presence of preceding events; time from symptom onset to nadir; occurrence of facial paralysis, bulbar paralysis, autonomic dysfunction ; requirement for mechanical ventilation; and form of treatment. Protein level and white blood cell count in the cerebrospinal fluid were also analyzed.Each patient's degree of motor disability was assessed according to Hughes functional grading   at nadirPatients with GBS were stratified according to the timing of symptom presentation from disease onset : the acuWe recorded the SSR from both the left and right palmar and plantar surfaces according to the Technical Standards of the International Federation of Clinical Neurophysiology . RecordiAll procedures were performed on the upper and lower limbs. Motor nerve conduction studies (MNCSs) were performed on the median, ulnar, tibial, and peroneal nerves. F-waves were examined in the median, ulnar, and tibial nerves. Sensory nerve conduction studies of the median, ulnar, and sural nerves were performed. The parameters included distal motor latency, distal and proximal compound muscle action potentials, motor and sensory conduction velocity, and minimal F-wave latency. GBS patients were classified as having AIDP or AMAN based on the criteria described by Hughes et al. .p-value of 0.05 was significant.Statistical analyses were performed using IBM SPSS Statistics version 24 . The distribution of all continuous variables was tested using the Kolmogorov–Smirnov normality test. Normally distributed continuous variables are reported in the form mean ± SD and were compared using the unpaired Student's t test. Non-normally distributed continuous variables are reported in the form of the median and interquartile range (IQR) and were compared using the Mann–Whitney U test. Categorical variables relating to clinical characteristics are reported in the form of proportions and were compared using the chi-square test or Fisher's exact probability test. Comparisons of SSR and NCS results obtained at early diagnosis of GBS and at follow-up were performed using McNemar's test. A A total of 27 children with GBS met the inclusion criteria: one patient with a pharyngeal-cervical-brachial subtype and one with a paraparetic subtype were excluded, and the remaining 25 children with GBS  were recruited; of these 21, had AIDP and 4 had AMAN, and the median age was 6 years (IQR = 5–8).Among the GBS group, 17 patients (66.7%) had AD, including nine with tachycardia, two with hypertension, four with urinary retention, and six with sudomotor dysfunction. Additionally, 18 patients (72%) exhibited an abnormal SSR, among whom 13 (52%) had autonomic dysfunction along with abnormal SSR findings, while five (20%) had SSR abnormalities only. In addition, six patients (24%) required mechanical ventilation, including five patients with AD and an abnormal SSR.The HCs consisted of 30 patients  with a median age of 11 years (IQR = 8–12). SSR could be elicited in all HCs, and the median onset latency of the SSR was 1.21 s (IQR = 1.15–1.24) in the upper limbs and 1.69 s (IQR = 1.65–1.77) in the lower limbs.P < 0.05). Overall, SSR abnormalities were more frequent in the GBS group than in the HCs . Twenty-three patients also underwent neuroelectrophysiological examinations in the progressive phase (median time since disease onset: 20 days). In this phase, the SSR changed from the absence of a waveform to a response with a prolonged latency, or the prolonged latency was gradually shortened. Finally, all GBS patients underwent neuroelectrophysiological tests in the recovery phase (median time since disease onset: 50 days); in this phase, the latency of the SSR was further shortened until it returned to baseline , and these showed absence of the SSR or prolonged latency. In these tests, eight patients 32%) had an absent SSR in the upper and lower limbs simultaneously, three patients (12%) exhibited prolonged latency in the upper and lower limbs, and seven patients (28%) exhibited prolonged latency in the lower limbs only. SSR latencies (including onset and N latency) in the lower limbs were significantly longer in the GBS group than in the HCs (% had an baseline .P = 0.727). In addition, there were six patients (24%) with abnormal SSR and 17 patients (68%) with abnormal NCS findings in the recovery phase, and recovery of SSR occurred earlier than that of NCS during the follow-up period in GBS (P = 0.003)  had an abnormal SSR and 16 patients (64%) had NCS abnormalities; the SSR abnormalities did not differ statistically from the NCS abnormalities among the GBS patients (= 0.003) .P > 0.05). Neither CSF counts (proteins and white blood cells) nor duration of hospitalization differed significantly between these two groups (P > 0.05). The abnormal SSRs mainly in patients with AIDP subtype, although the difference between the two groups in electrophysiological subtype (AIDP vs. AMAN) was not statistically significant (P = 0.548), but abnormal SSRs occurred mainly in patients with the AIDP subtype. Seven GBS patients (28%) had a poor prognosis 1 month after symptom onset, and the SSR of all these patients was abnormal. All children with GBS had a good prognosis 6 months after onset , gastrointestinal dysfunction , and excessive sweating . ConsistOne cohort study of pediatric GBS complicated by AD has shown that AD is significantly associated with increased severity and poor prognosis of GBS . In the The limitations of our study are as follows. First, we mainly analyzed latency of SSR, without considering amplitude. In future studies, our team will analyze the amplitude of SSR and improve the study of SSR in GBS. Second, the sample size was small. Thus, we will enroll more children in the future to better investigate the association between SSR and short- or long-term prognosis in children with GBS.In conclusion, children with GBS have a higher incidence of AD. Sympathetic skin response is a useful electrophysiological tool for assessment of AD and could be used for the early diagnosis and follow-up of GBS; it may also be slightly helpful in evaluating disease severity and short-term prognosis.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.This study was approved by the Ethics Committee of the Children's Hospital of Hebei Province. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.JL and LZ acquired the electrophysiological data. KL and ZZ acquired clinical data and conducted the statistical analysis. MJ designed the experiments, interpreted the results, and drafted the manuscript. SS revised the initial draft and wrote the final version of the manuscript. All authors made a significant contribution to the work and approved the manuscript.


However, a systematic synthesis of the aspects that are important to patients regarding the quality of GR does not exist.the aim of this scoping review was to systematically synthesise the patients’ perspective on the quality of GR.we followed the Scoping Review framework and gathered literature including a qualitative study design from multiple databases. The inclusion criteria were: a qualitative study design; a geriatric population; that patients had participated in a geriatric rehabilitation programme and that geriatric rehabilitation was assessed by the patient. The results sections of the included studies were analysed using a thematic analysis approach.twenty articles were included in this review. The main themes identified were: (i) the need for information about the rehabilitation process, (ii) the need for telling one’s story, (iii) the need for support , (iv) the need for shared decision-making and autonomy, (v) the need for a stimulating rehabilitation environment and (vi) the need for rehabilitation at home.in this study, we identified the aspects that determine the quality of rehabilitation from the patient’s perspective, which may lead to a more holistic perspective on the quality of GR. This review presents the first steps into identifying the range of themes/aspects that patients consider important when in geriatric rehabilitation.More attention to the questions and needs of the patient might ensure that rehabilitation will be better adapted to the patients’ preferences and needs.Future research should focus on how best to assess patients’ experiences in the different phases of rehabilitation and how care teams can use these experiences to improve the quality of geriatric rehabilitation.et al. [Globally, the size of the population that are aged 65 years and older will rapidly increase in the upcoming decades and is estimated to reach over 1.5 billion in 2050 . After het al.  mentionset al. . Geriatret al. . Patientet al. . The maiet al. , 13. GR et al. .The efficacy and outcomes of GR have been well investigated . There iThe inclusion of these perspectives is of utmost importance during the rehabilitation process, especially with regards to its effectiveness , 27.The aim of this scoping review (ScR) is to systematically synthesise the quality of GR from the patient perspective. More specifically, we seek to answer the following research question: from the patients’ perspective, what is important for the quality of geriatric rehabilitation? To answer this question, we will review qualitative studies that address the quality of GR from the patient’s point of view.et al. [et al. [et al. [We followed the ScR framework outlined by Arksey and O’Malley , refinedet al. , Colquho [et al.  and Daud [et al. . We also [et al. . The pro [et al. .Embase.com, Clarivate Analytics/Web of Science Core Collection, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and the Cochrane Library. The search timeframe within the databases was from inception to 20th July 2022 and was conducted by G.B.L. and A.L. The search included the following keywords and free text terms: for (synonyms of) ‘rehabilitation’ or ‘physiotherapy’ combined with (synonyms of) ‘rehabilitation centre’ or ‘nursing home’ combined with (synonyms of) ‘geriatric population’ or ‘elderly’ combined with (synonyms of) ‘quality indicators’ combined with (synonyms of) ‘patient perspective’ or ‘self-reporting’ combined with (synonyms of) ‘qualitative research’. A full overview of the search terms used for each database can be found in A systematic search was performed across the following databases: PubMed, Study selection took place over two steps. In the first step, two team members (A.L. and S.H.) independently assessed the titles and abstracts relevant to the research question against the inclusion criteria. A.L. and S.H. agreed to include a study for full text screening when they could not determine its relevance based on the abstract and title alone. In the second step, potentially relevant studies were assessed on their full text by means of applying the selection criteria (A.L.). If there was uncertainty, a second team member (M.R./M.P.) was asked to review the article. In the case of disagreement, consensus was sought through additional discussions.The inclusion criteria were:A qualitative study design.Includes a geriatric population (age).Patients participating in a geriatric rehabilitation program.Aspects of the quality of geriatric rehabilitation assessed by the patient themselves.Articles in either Dutch or English.Articles were excluded if they contained:Patients permanently living in long-term care, without a programme for geriatric rehabilitationAny patient < 55 years and/or with a mean age < 60 yearsA data extraction form was developed by A.L. to identify the variables from the included articles and was piloted on five articles by the reviewers . In the extraction form, we collected the relevant information for the scoping review, specifically the patients’ point of view regarding the quality of GR, which was divided into possible categories such as aim, patient perspective, quality of care, quality of life, key findings and GR assessment. The extraction form was completed by A.L. If there was any doubt, M.R./M.P. were consulted for consensus. The extraction form can be found in We performed a qualitative synthesis  to classThe process of study selection is depicted in a PRISMA Flow Diagram . In thisThe sample size of the participants in the studies ranged from 5 to 53 participants. Manuscripts were published across eight different countries and were published from 1999 to 2019, with 12 of the studies published after 2015. All included articles were peer-reviewed journal articles. Further information about the included studies is presented in et al. [et al. [The mean age of the patients varied from 60.8 to 81.4 years. There was a large variety of diagnoses across the participants; (i) four articles focused on hip fractures , 37, 52,et al.  consider [et al.  describeThe open coding of the results sections of the 20 included articles led to a set of codes. These codes were grouped into an initial set of themes. This initial set of themes was discussed amongst the project group which resulted in the following themes related to the quality of GR from a patient’s perspective: (i) the need for information about the rehabilitation process, (ii) the need for telling one’s story, (iii) the need for support , (iv) the need for shared decision-making and autonomy, (v) the need for a stimulating rehabilitation environment and (vi) the need for rehab in the home. These themes will be addressed below.Patients reported a lack of information throughout the rehabilitation process. Several studies find that patients experience a lack of information about the rehabilitation process at the beginning of GR , 44–50. Letting patients tell their story is the first step in rehabilitation . Being aHaving support from professionals provided comfort and made patients feel that they had learnt about their rehabilitation. The consistent delivery of care promoted this . RehabilDuring rehabilitation, patients experience various limitations in their functioning and need support for this. These needs as perceived by the patients can be divided into four different categories.Patients experienced limitations because of what they had gone through, and these limitations had not been fully overcome after intramural rehabilitation. In the home setting, patients still experienced a lack of energy, so they had to ask for more help and required more rest. Pain and mobility limitations played a role in daily life and although physical functioning improved, these limitations remained , 46.Psychological factors were not always included in the rehabilitation process . Being cCoping can play a major role in how rehabilitation progresses . For exaThe main goal of rehabilitation for the patient is to be able to participate in society . HoweverA patient’s level of autonomy changes during rehabilitation: as discharge approaches, it shifts from passive to active, whereby patients interact more with the rehabilitation process . PatientPreferences must be discussed in the rehabilitation process: an example of this is analysing the problems and strengths the patient has, and how to apply them to solve their issues . For strPatients reported that shared decision-making during goal setting was very important to them. Patients involved in goal setting and planning of their rehabilitation experience reported being more satisfied with their long-term self-care and were better able to self-manage . Being aThe atmosphere in a rehabilitation setting is experienced differently than in a hospital . One difAfter discharge, patients may still need rehabilitation support, for which contact with follow-up care institutions is important. For a patient, planning and arranging contact with care and municipal services is a major task . A team Many patients experienced discharge as very difficult . A lack Rehabilitation is often aimed at improving functioning, however pre-hospitalisation functioning may not yet have been achieved at the moment of discharge. If patients function at a basic ADL level, they are usually discharged and are able to function at home . Some paThe aim of this study was to systematically synthesise patients’ perspectives on the quality of GR. In this scoping review, 20 qualitative studies were included. Six themes resulting from this scoping review reflect the patient’s perspective as to the quality of geriatric rehabilitation care: (i) the need for information about the rehabilitation process, (ii) the need for telling one’s story, (iii) the need for support , (iv) the need for shared decision-making and autonomy, (v) the need for a stimulating rehabilitation environment and (vi) the need for rehabilitation in the home setting.et al. [et al. [Many of these themes have been found to be important in previous studies on the quality of medical rehabilitation. Giesler et al.  and Niel [et al.  also fouet al. [Janssen et al.  examinedet al. [et al. However, it does contribute to patient satisfaction, which is considered valuable from a professional perspective [The elements defined by Janssen et al.  and the spective . The impspective . In addispective , but thispective . A compaWhat this study adds are elements on the quality of rehabilitation from the patient’s perspective, which can lead to a more holistic perspective on quality. This scoping review contributes an overview of the knowledge from the perspective of the patient. To date, GR has mainly been described from the perspective of the professionals. Patients should be given space to share their care experiences in a way that they feel comfortable. Focusing on meaningful care experiences as a whole can contribute to a new way of assessing the experienced quality of care . The patThe perspectives of the geriatric patient have only been measured at one point in time in all of the included studies , 35–53, A strength of this scoping review is the in-depth and comprehensive summary of qualitative studies performed on patients undergoing geriatric rehabilitation. The review of qualitative research best reflects the patient’s perspective on the quality of geriatric rehabilitation. This provides the basis for further research to increase the quality of GR, with the acknowledgement that rehabilitation is a process that could change over time. This study complements the overview on the quality of rehabilitation care from different perspectives through the addition of the patient perspective. However, this study has some limitations that might impact its generalisability.First, the restriction of publication languages to Dutch and English could have limited the generalisability of our findings; there may be additional information written in a language other than English or Dutch. Second, we observed that in total, only two studies included participants with cognitive impairment. Therefore, the current results are not generalisable to older people with severe cognitive impairment. It is important to know how these patients think about what is important regarding the quality of GR and future research should address this remaining uncertainty. Third, we aimed to include studies on in- and outpatient rehabilitation. However, the results show that the majority of studies are conducted among patients who are treated in the inpatient setting. Therefore, the outpatient setting also should be further studied. Finally, 8 of the 20 included studies are about stroke patients, making the results less generalisable to the entire GR population.The information obtained is from summarised findings of qualitative studies and not from the primary data, which can be seen as a limitation. However, to create a concise overview of the data, we did not think it was necessary to use the original data.This scoping review identified six themes reflecting the patient’s perspective as to the quality of geriatric rehabilitation: (i) the need for information about the rehabilitation process, (ii) the need for telling one’s story, (iii) the need for support , (iv) the need for shared decision-making and autonomy, (v) the need for a stimulating rehabilitation environment and (vi) the need for rehabilitation in the home setting.Involving the patient perspective when defining the quality of GR may improve the experienced quality of GR for both patients and health care professionals, thus contributing to a more holistic perspective on quality.This review presents the first steps into identifying the range of themes/aspects that patients consider important in GR. To achieve a high-quality care experience in rehabilitation, future research should focus on how to best assess patients’ experiences in the different phases of rehabilitation, on including people with cognitive impairment, on the outpatient setting and on how care teams can use these experiences to improve the quality of GR.aa-22-1755-File002_afad032Click here for additional data file.aa-22-1755-File003_afad032Click here for additional data file.