A taxonomic backbone for the Plumbaginaceae (Caryophyllales).

A taxonomic backbone of the Plumbaginaceae is presented and the current state of knowledge on phylogenetic relationships and taxon limits is reviewed as a basis for the accepted taxon concepts. In total, 4,476 scientific names and designations are treated of which 30 are not in the family Plumbaginaceae. The Plumbaginaceae are subdivided in three tribes with 26 genera and 1,179 accepted species. Two subgenera, 17 sections, two subsections and 187 infraspecific taxa are accepted. At the species and infraspecific level 2,782 synonyms were assigned to accepted taxa, whereas 194 names were excluded from the core checklist (i.e., unplaced taxa, infrageneric subdivisions with still uncertain application, names of verified uncertain application, invalid horticultural names, excluded names from other families, other excluded designations, and unresolved names). The EDIT Platform for Cybertaxonomy was utilized as the tool to compile and manage the names and further taxonomic data under explicit taxon concepts. Secundum references are given in case taxon concepts were taken from the literature, whereas this study serves as reference for newly circumscribed taxa. The family's division into the tribes Aegialitideae, Limonieae, and Plumbagineae departs from earlier two-subfamily classifications, prompted by recent phylogenetic findings that challenge the subfamilial affinity of Aegialitis. The genus Acantholimon was extended to include Gladiolimon, as currently available phylogenetic and morphological data support this merger. In Limonium, all accepted species could be assigned to sections and subsections or the "Mediterranean lineage", respectively, making use of the phylogenetic distribution of their morphological characters and states. A new combination and/or status is proposed for Dyerophytumsocotranum, Limoniumthymoides, Limonium×fraternum, Limonium×rossmaessleri, and Limoniumsect.Jovibarba. Special attention is given to nomenclatural issues, particularly for Staticenomenambiguum to resolve the names under accepted names. The use of artificial groupings like "aggregates", "complexes" and "species groups" in alpha-taxonomic treatments is discussed. The taxonomic backbone will receive continued updates and through the Caryophyllales Taxonomic Expert Network, it contributes the treatment of the Plumbaginaceae for the World Flora Online.

Landscape features influencing gene flow and connectivity of an endangered passerine.

Dispersal of individuals and gene flow are crucial aspects to maintain genetic diversity and viability of populations, especially in the case of threatened species. Landscape composition and structure may facilitate or limit individual movement within and among populations. We used a landscape genetics approach to assess the connectivity patterns of the threatened Dupont's lark (Chersophilus duponti subsp. duponti), considering their genetic patterns and the landscape features associated with its gene flow in Spain. We analysed the genetic relatedness based on 11 species-specific polymorphic microsatellites on 416 Dupont's lark individuals sampled across peninsular Spain between 2017 and 2019, covering most of the European distribution of the species. To assess the relationship between the landscape composition and the species gene flow, we estimated genetic distance at the individual level (Dps). Next, we built a set of environmental surfaces from two time periods (years 1990 and 2018), based on factors such as land use and topography, influencing individuals' movement. We then obtained resistance surfaces from an optimization process on landscape variables. Landscape genetics analyses were done for single and composite surface models for each year separately. Our findings from both time points show that scatter or mosaic-structured vegetation composed by low agricultural and tree cover and high presence of sclerophyllous shrubs favoured Dupont's lark dispersal, while dense and continuous tree cover, as well as areas of intensive agriculture, were limiting factors. Our results suggest the importance of steppe habitat patches for the species' establishment and dispersal. In addition, our results provide key information to develop conservation measures, including conserving and restoring steppe habitats as scattered and/or mosaic-structured vegetation that could warrant the connectivity and persistence of Dupont's lark populations.

Study protocol: improving response to malaria in the Amazon through identification of inter-community networks and human mobility in border regions of Ecuador, Peru and Brazil.

INTRODUCTION: Understanding human mobility's role in malaria transmission is critical to successful control and elimination. However, common approaches to measuring mobility are ill-equipped for remote regions such as the Amazon. This study develops a network survey to quantify the effect of community connectivity and mobility on malaria transmission. METHODS: We measure community connectivity across the study area using a respondent driven sampling design among key informants who are at least 18 years of age. 45 initial communities will be selected: 10 in Brazil, 10 in Ecuador and 25 in Peru. Participants will be recruited in each initial node and administered a survey to obtain data on each community's mobility patterns. Survey responses will be ranked and the 2-3 most connected communities will then be selected and surveyed. This process will be repeated for a third round of data collection. Community network matrices will be linked with each country's malaria surveillance system to test the effects of mobility on disease risk. ETHICS AND DISSEMINATION: This study protocol has been approved by the institutional review boards of Duke University (USA), Universidad San Francisco de Quito (Ecuador), Universidad Peruana Cayetano Heredia (Peru) and Universidade Federal Minas Gerais (Brazil). Results will be disseminated in communities by the end of the study.

The Lure of the Podium: The Seductive Appeal of Predatory Conference Speaker Invitations.

This letter highlights an escalating concern regarding predatory conference speaker invitations that are currently plaguing academia. Such invitations are frequently issued to individuals outside their areas of expertise, for instance, non-healthcare professionals being invited to health-related conferences. This issue poses a substantial threat as it compromises the integrity of legitimate academic discourse and carries the risk of propagating unchecked and potentially detrimental information. To avoid becoming ensnared by these predatory practices, it is paramount to undertake thorough due diligence. Consequently, this letter also outlines the characteristics of predatory speaker invitations. These guidelines underscore the necessity for the academic community to remain vigilant and judicious, thereby recognizing these overtures for what they truly represent: a deceptive temptation that leads away from authentic scholarly engagement toward a facade of recognition and prestige.

Regulation of Epithelial and Endothelial Barriers by Molecular Chaperones.

The integrity and permeability of epithelial and endothelial barriers depend on the formation of tight junctions, adherens junctions, and a junction-associated cytoskeleton. The establishment of this junction-cytoskeletal module relies on the correct folding and oligomerization of its protein components. Molecular chaperones are known regulators of protein folding and complex formation in different cellular compartments. Mammalian cells possess an elaborate chaperone network consisting of several hundred chaperones and co-chaperones. Only a small part of this network has been linked, however, to the regulation of intercellular adhesions, and the systematic analysis of chaperone functions at epithelial and endothelial barriers is lacking. This review describes the functions and mechanisms of the chaperone-assisted regulation of intercellular junctions. The major focus of this review is on heat shock protein chaperones, their co-chaperones, and chaperonins since these molecules are the focus of the majority of the articles published on the chaperone-mediated control of tissue barriers. This review discusses the roles of chaperones in the regulation of the steady-state integrity of epithelial and vascular barriers as well as the disruption of these barriers by pathogenic factors and extracellular stressors. Since cytoskeletal coupling is essential for junctional integrity and remodeling, chaperone-assisted assembly of the actomyosin cytoskeleton is also discussed.

Risk of Primary Gastrointestinal Lymphoma in Patients With Inflammatory Conditions Exposed to Tumor Necrosis Factor Alpha Inhibitors and Immunomodulators: A Case-Control Study.

Introduction: The aim of this case-control study was to determine if exposure to tumor necrosis factor alpha inhibitors (TNFIs) or immunomodulators (thiopurines or methotrexate) was associated with development of primary gastrointestinal lymphoma (PGIL) in patients with chronic inflammatory conditions. Methods: Patients with PGIL and controls evaluated at a tertiary care center over 20 years were matched 1:3 using a medical record informatics search engine based on their chronic inflammatory condition (Crohn's disease [CD], ulcerative colitis [UC], rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis) and duration of follow-up. Patients who started on TNFI within 3 months of PGIL diagnosis were excluded. We extracted demographics, medical history, and medications used. Univariate models using conditional logistic regression were used due to the small number of matched pairs. Results: Twenty PGIL cases matched with 60 controls were followed for a mean 9.9 ±â€…6.9 and 9.7 ±â€…8.6 years, respectively. Mean age at time of PGIL diagnosis was 47.5 ±â€…22.0 (standard deviation) years and the majority (75%) were males. The most common inflammatory diagnosis was inflammatory bowel disease (80% of cases; 45% with UC and 35% with CD). Development of PGIL was not associated with TNFI (odds ratio [OR] = 2.6; 95% confidence interval [CI] 0.69-11.01; P = .18), but with use of TNFI in combination with thiopurines (OR = 8.93; 95% CI 1.43-80.25; P = .014). Risk of PGIL increased with every additional TNFI (2.277 (1.002-5.713); P = .0494). All cases exposed to multiple TNFI were also exposed to thiopurines. Use of thiopurines (alone or in combination) was the greatest risk factor (OR = 6.32; 95% CI 1.55-37.05; P = 0.006) to develop PGIL. Conclusions: TNFI therapy was not associated with increased risk for PGIL unless used in combination with thiopurines and with every switch to a different TNFI.

Intussusception in Mosaic Trisomy 14.

Mosaic trisomy 14 is exceptionally rare and was first described in the 1970s with fewer than 100 known liveborn individuals. Information about complications and the natural history of the disease is rare, especially in adult patients. This case illustrates an adult patient with severe functional limitations from mosaic trisomy 14 who presented with abdominal pain and failure to thrive and was subsequently found to have intussusception and severe chronic constipation, which was successfully treated conservatively.

PathoGraph: An Attention-Based Graph Neural Network Capable of Prognostication Based on CD276 Labelling of Malignant Glioma Cells.

Computerized methods have been developed that allow quantitative morphological analyses of whole slide images (WSIs), e.g., of immunohistochemical stains. The latter are attractive because they can provide high-resolution data on the distribution of proteins in tissue. However, many immunohistochemical results are complex because the protein of interest occurs in multiple locations (in different cells and also extracellularly). We have recently established an artificial intelligence framework, PathoFusion which utilises a bifocal convolutional neural network (BCNN) model for detecting and counting arbitrarily definable morphological structures. We have now complemented this model by adding an attention-based graph neural network (abGCN) for the advanced analysis and automated interpretation of such data. Classical convolutional neural network (CNN) models suffer from limitations when handling global information. In contrast, our abGCN is capable of creating a graph representation of cellular detail from entire WSIs. This abGCN method combines attention learning with visualisation techniques that pinpoint the location of informative cells and highlight cell-cell interactions. We have analysed cellular labelling for CD276, a protein of great interest in cancer immunology and a potential marker of malignant glioma cells/putative glioma stem cells (GSCs). We are especially interested in the relationship between CD276 expression and prognosis. The graphs permit predicting individual patient survival on the basis of GSC community features. Our experiments lay a foundation for the use of the BCNN-abGCN tool chain in automated diagnostic prognostication using immunohistochemically labelled histological slides, but the method is essentially generic and potentially a widely usable tool in medical research and AI based healthcare applications.

Temporal trends of land-use favourability for the strongly declining little bustard: assessing the role of protected areas.

The little bustard (Tetrax tetrax) is a steppe bird strongly and negatively influenced by agricultural intensification in Europe. Here, we use the little bustard as a model species to examine how favourability (relative occurrence likelihood of a species based on environmental characteristics, such as habitat availability) varies regionally with degree of protection in north-western Spain. The Natura2000 network is one of the main biodiversity conservation tools of the European Union, aiming to protect areas hosting species of conservation concern from unfavourable land-use changes. The network covers many landscapes across the continent, including farmland. Additionally, we examine the relationship between trends in land-use favourability and little bustard population trends over a decade in the Nature Reserve of Lagunas de Villafáfila, a protected area also in the Natura2000 network where active and intense management focused on steppe bird conservation is carried out. Favourability was much greater in Villafáfila than in both protected areas with lower degree of protection and in non-protected areas. Land-use favourability increased slightly between 2011 and 2020 both in and out of protected areas, whereas little bustard populations declined sharply in that period, even in Villafáfila. Spatial variations in little bustard abundance within Villafáfila depended on social attraction (increasing with the number of neighbouring males) but not significantly on small-scale variations in land-use favourability. These results suggest that land-use management in Natura2000 areas needs to be more conservation-focused, favouring natural and seminatural habitats and traditional farming practices to improve land-use favourability for little bustards and other steppe birds. Additional factors, such as field-level agricultural management or social interaction variables that may cause an Allee effect, should be incorporated in little bustard favourability models to improve their use in conservation planning.

Using AI Tools in Writing Peer Review Reports: Should Academic Journals Embrace the Use of ChatGPT?

This letter highlights a pressing issue regarding the absence of established editorial policies for the utilization of AI tools (e.g., ChatGPT) in the peer review process. The increasing adoption of AI tools in academic publishing necessitates the formulation of standardized guidelines to ensure fairness, transparency, and accountability. Without clear editorial policies, there is a threat of compromising the integrity of the peer review process and undermining the credibility of academic publications. Urgent attention is needed to address this gap and establish robust protocols that govern the use of AI tools in peer review.

Network Profile: Improving Response to Malaria in the Amazon through Identification of Inter-Community Networks and Human Mobility in Border Regions of Ecuador, Peru, and Brazil.

Objectives: Understanding human mobility's role on malaria transmission is critical to successful control and elimination. However, common approaches to measuring mobility are ill-equipped for remote regions such as the Amazon. This study develops a network survey to quantify the effect of community connectivity and mobility on malaria transmission. Design: A community-level network survey. Setting: We collect data on community connectivity along three river systems in the Amazon basin: the Pastaza river corridor spanning the Ecuador-Peru border; and the Amazon and Javari river corridors spanning the Brazil-Peru border. Participants: We interviewed key informants in Brazil, Ecuador, and Peru, including from indigenous communities: Shuar, Achuar, Shiwiar, Kichwa, Ticuna, and Yagua. Key informants are at least 18 years of age and are considered community leaders. Primary outcome: Weekly, community-level malaria incidence during the study period. Methods: We measure community connectivity across the study area using a respondent driven sampling design. Forty-five communities were initially selected: 10 in Brazil, 10 in Ecuador, and 25 in Peru. Participants were recruited in each initial node and administered a survey to obtain data on each community's mobility patterns. Survey responses were ranked and the 2-3 most connected communities were then selected and surveyed. This process was repeated for a third round of data collection. Community network matrices will be linked with eadch country's malaria surveillance system to test the effects of mobility on disease risk. Findings: To date, 586 key informants were surveyed from 126 communities along the Pastaza river corridor. Data collection along the Amazon and Javari river corridors is ongoing. Initial results indicate that network sampling is a superior method to delineate migration flows between communities. Conclusions: Our study provides measures of mobility and connectivity in rural settings where traditional approaches are insufficient, and will allow us to understand mobility's effect on malaria transmission.

Nomenclatural Type Identification of Names in North African Tamarix (Tamaricaceae).

Tamarix is native to Eurasia plus the northern and southern territories of Africa, with some species being introduced into America and Oceania. They are usually found in arid, desertic, or subdesertic areas, often on saline or subsaline soils, in Mediterranean, temperate, or subtropical climates. The genus is renowned for its complex taxonomy, which is usually based on rather variable or unstable characters, which leads to contrasting taxonomic treatments. As part of the taxonomic revision of Tamarix undertaken by the authors, ten names (i.e., T. africana, T. bounopoea, T. brachystylis var. fluminensis, T. malenconiana, T. muluyana, T. tenuifolia, T. tingitana, T. trabutii, T. valdesquamigera, and T. weyleri) published from material collected in the southwestern parts of the Mediterranean basin are taxonomically and nomenclaturally discussed after analysing their original material. Eight intended holotypes are corrected here to lectotypes; one epitype is designated for T. africana to warrant current use of the name; and one isotype, 30 isolectotypes, and 11 syntypes are also identified for the studied names. Further, the taxonomic identity of all names and their eventual synonymic placement are accordingly discussed.

Effective ventilation and chest compressions during neonatal resuscitation - the role of the respiratory device.

BACKGROUND: The success of cardiopulmonary resuscitation (CPR) in newborns largely depends on effective lung ventilation; however, a direct randomized comparison using different available devices has not yet been performed. METHODS: Thirty-six professionals were exposed to a realistic newborn CPR scenario. Ventilation with either a bag-valve mask (BVM), T-piece, or ventilator was applied in a randomized manner during CPR using a Laerdal manikin. The primary outcome was the number of unimpaired inflations, defined as the peak of the inflation occurring after chest compression and lasting at least 0.35 s before the following chest compression takes place. The secondary outcomes were tidal volume delivered and heart compression rate. To simulate potential distractions, the entire scenario was performed with or without a quiz. Statistically, a mixed model assessing fixed effects for experience, profession, device, and distraction was used to analyze the data. For direct comparison, one-way ANOVA with Bonferroni's correction was applied. RESULTS: The number of unimpaired inflations was highest in health care professionals using the BVM with a mean ± standard deviation of 12.8 ± 2.8 (target: 15 within 30 s). However, the tidal volumes were too large in this group with a tidal volume of 42.5 ± 10.9 ml (target: 25-30 ml). The number of unimpaired breaths with the mechanical ventilator and the T-piece system were 11.6 (±3.6) and 10.1 (±3.7), respectively. Distraction did not change these outcomes, except for the significantly lower tidal volumes with the T-piece during the quiz. CONCLUSIONS: In summary, for our health care professionals, ventilation using the mechanical ventilator seemed to provide the best approach during CPR, especially in a population of preterm infants prone to volutrauma.

Liver Injury after Selective Androgen Receptor Modulator Intake: A Case Report and Review of the Literature.

Liver injury associated with selective androgen receptor modulators (SARMs) is an issue that has not been reported often. We report a case of a previously healthy 24-year-old male, who was referred to our hospital for severe jaundice with intense pruritus. He had previously taken the SARM Enobosarm (also known as Ostarine) for muscle-building purposes. Blood serum levels of total bilirubin exceeded 30 mg/dL with only a slight elevation of liver enzymes. Liver biopsy revealed isolated hepatocellular cholestasis (bland cholestasis) with limited inflammation or necrosis. Supportive treatment was begun in our hospital with molecular adsorbent recirculation system (MARS) albumin dialysis, as well as cholestyramine for pruritus relief. During therapy, bilirubin levels and symptoms regressed, and after five sessions of dialysis, the patient could be released from our clinic in a markedly improved clinical and laboratory condition. However, bilirubin parameters regressed slowly after this, reaching normal levels as late as six months after first intake of the compound. Exome-based genetic testing brought about no pathogenic variants for cholestatic liver disease in our patient. Nevertheless, three common heterozygous polymorphisms associated with an increased risk for intrahepatic cholestasis could be identified. Our case demonstrates that SARMs can cause severe liver injuries not prominently mentioned in safety data sheets. Therefore, these compounds constitute a potential danger to the user's health. This holds especially true when taking SARMs without supervision by a medical professional, which should consist of a thorough monitoring of liver enzyme and bilirubin levels.

Neuroinflammation: The Abused Concept.

Scientific progress requires the relentless correction of errors and refinement of hypotheses. Clarity of terminology is essential for clarity of thought and proper experimental interrogation of nature. Therefore, the application of the same scientific term to different and even conflicting phenomena and concepts is not useful and must be corrected. Such abuse of terminology has happened and is still increasing in the case of "neuroinflammation," a term that until the 1990s meant classical inflammation affecting the central nervous system (CNS) and thereon was progressively used to mostly denote microglia activation. The resulting confusion is very wasteful and detrimental not only for scientists but also for patients, given the numerous failed clinical trials in acute and chronic CNS diseases over the last decade with "anti-inflammatory" drugs. Despite this failure, reassessments of the "neuroinflammation" concept are rare, especially considering the number of articles still using the term. This undesirable situation motivates this article. We review the origins and evolution of the term "neuroinflammation," discuss the unique tissue defense and repair strategies in the CNS, define CNS immunity, and emphasize the notion of gliopathies to help readdress, if not bury, the term "neuroinflammation" as it stands in the way of scientific progress.

What Is Wrong with Frankenia nodiflora Lam. (Frankeniaceae)? New Insights into the South African Sea-Heaths.

The taxonomic identity and phylogenetic relationships of several southern African perennial taxa related to Frankenia repens are discussed. In particular, F. nodiflora Lam., a misunderstood species described from the Cape region and synonymised to F. pulverulenta, is restored for plants endemic to salt-pans and riverbeds in the coastal lowlands across the Cape Flats (Western Cape province, South Africa). Further, a revision of morphologically close plants, usually identified as F. pulverulenta or F. repens, also occurring in similar saline ecosystems of the inland western South Africa revealed the existence of two distinct new entities not matching any described taxa of the genus. Molecular analyses of nuclear ribosomal (ITS1-5.8S-ITS2 region) DNA sequence data together with morphological divergence allow recognition of those taxa at species rank, within an independent lineage close to F. repens. In consequence, two new sea-heath species are described in the so-called "F. repens group": F. nummularia from the Nama-Karoo Biome (Western Cape and Northern Cape provinces), and F. anneliseae from the Succulent Karoo Biome (Northern Cape province). Full morphological description and type designation are reported for each accepted species as well as data on ecology, habitat, distribution, and taxonomic relationships to other close relatives are given. Further, an identification key is presented to facilitate recognition of the southern African taxa of Frankenia.

Spergularia hanoverensis (Caryophyllaceae): Validation and Recircumscription of a Misinterpreted Species from South Africa.

The name "Spergularia hanoverensis Simon" has been misapplied to an endemic taxon confined to inland semidesert ecosystems in central-western South Africa. It is commonly accepted as a small annual species occurring in saline habitats in a wide elevation range, but its identity still remains obscure. In the context of taxonomic and phylogenetic research on the African species of Spergularia, we found that the name was never validly published. After revision of herbarium material housed in South African herbaria, a voucher collected from Hanover was found at PRE bearing some labels handwritten by E. Simon that suggest it might be an intended type for the name. Additional herbarium material and wild populations from the Karoo region were identified that matched the samples in that voucher, and taxonomic research was conducted to clarify their identity. Among other characters, those Karoo plants show a woody dense compact habit, woody perennial at base; stems prostrate to ascendent; leaves entirely glabrous, somewhat glaucous; large white-hyaline conspicuous stipules; inflorescence glanduliferous, many-flowered subdichasial cyme, with minute bracts; flowers small, with white petals approximately equalling sepals in length, stamens 7-8, and styles free from base; capsule small, with seeds dimorphic, unwinged to broadly winged, with testa always densely tuberculate. Molecular analyses of plastid (trnL-trnF region) and nuclear ribosomal (5.8S-ITS2 region) DNA sequence data support morphological differentiation of the Karoo plants, for which the name S. hanoverensis is here effectively published. A full morphological description and data on ecology, habitat, distribution, and taxonomic and phylogenetic relationships of S. hanoverensis are compared to other members of the "South African group", namely S. glandulosa, S. namaquensis, and S. quartzicola, from which the new species considerably differs. The adaptative significance of dimorphic seeds of S. hanoverensis is briefly commented on in the context of the species habitat preference. An identification key is presented for the South African related taxa.

κO-SrVIA Conopeptide, a Novel Inhibitor Peptide for Two Members of the Human EAG Potassium Channel Family.

The first conotoxin affecting the voltage-gated potassium channels of the EAG family was identified and characterized from the venom of the vermivorous species Conus spurius from the Gulf of Mexico. This conopeptide, initially named Cs68 and later designated κO-SrVIA, is extremely hydrophobic and comprises 31 amino acid residues, including six Cysteines in the framework VI/VII, and a free C-terminus. It inhibits the currents mediated by two human EAG subtypes, Kv10.1 (IC50 = 1.88 ± 1.08 µM) and Kv11.1 (IC50 = 2.44 ± 1.06 µM), and also the human subtype Kv1.6 (IC50 = 3.6 ± 1.04 µM). Despite its clear effects on potassium channels, it shares a high sequence identity with δ-like-AtVIA and δ-TsVIA. Also, κO-SrVIA is the third conopeptide from the venom of C. spurius with effects on potassium channels, and the seventh conotoxin that blocks Kv1.6 channels.

Hypomethylation and Overexpression of Th17-Associated Genes is a Hallmark of Intestinal CD4+ Lymphocytes in Crohn's Disease.

BACKGROUND: The development of Crohn's disease [CD] involves immune cell signalling pathways regulated by epigenetic modifications. Aberrant DNA methylation has been identified in peripheral blood and bulk intestinal tissue from CD patients. However, the DNA methylome of disease-associated intestinal CD4+ lymphocytes has not been evaluated. MATERIALS AND METHODS: Genome-wide DNA methylation sequencing was performed from terminal ileum CD4+ cells from 21 CD patients and 12 age- and sex-matched controls. Data were analysed for differentially methylated CpGs [DMCs] and methylated regions [DMRs]. Integration was performed with RNA-sequencing data to evaluate the functional impact of DNA methylation changes on gene expression. DMRs were overlapped with regions of differentially open chromatin [by ATAC-seq] and CCCTC-binding factor [CTCF] binding sites [by ChIP-seq] between peripherally derived Th17 and Treg cells. RESULTS: CD4+ cells in CD patients had significantly increased DNA methylation compared to those from the controls. A total of 119 051 DMCs and 8113 DMRs were detected. While hypermethylated genes were mostly related to cell metabolism and homeostasis, hypomethylated genes were significantly enriched within the Th17 signalling pathway. The differentially enriched ATAC regions in Th17 cells [compared to Tregs] were hypomethylated in CD patients, suggesting heightened Th17 activity. There was significant overlap between hypomethylated DNA regions and CTCF-associated binding sites. CONCLUSIONS: The methylome of CD patients shows an overall dominant hypermethylation yet hypomethylation is more concentrated in proinflammatory pathways, including Th17 differentiation. Hypomethylation of Th17-related genes associated with areas of open chromatin and CTCF binding sites constitutes a hallmark of CD-associated intestinal CD4+ cells.