Separate Entity Research Articles

CollaPPI: A Collaborative Learning Framework for Predicting Protein-Protein Interactions.

Exploring protein-protein interaction (PPI) is of paramount importance for elucidating the intrinsic mechanism of various biological processes. Nevertheless, experimental determination of PPI can be both time-consuming and expensive, motivating the exploration of data-driven deep learning technologies as a viable, efficient, and accurate alternative. Nonetheless, most current deep learning-based methods regarded a pair of proteins to be predicted for possible interaction as two separate entities when extracting PPI features, thus neglecting the knowledge sharing among the collaborative protein and the target protein. Aiming at the above issue, a collaborative learning framework CollaPPI was proposed in this study, where two kinds of collaboration, i.e., protein-level collaboration and task-level collaboration, were incorporated to achieve not only the knowledge-sharing between a pair of proteins, but also the complementation of such shared knowledge between biological domains closely related to PPI (i.e., protein function, and subcellular location). Evaluation results demonstrated that CollaPPI obtained superior performance compared to state-of-the-art methods on two PPI benchmarks. Besides, evaluation results of CollaPPI on the additional PPI type prediction task further proved its excellent generalization ability.

Prognostic impact of SF3B1 mutation and multilineage dysplasia in myelodysplastic syndromes with ring sideroblasts: a Mayo Clinic study of 170 informative cases.

The revised 4th edition of the World Health Organization (WHO4R) classification lists myelodysplastic syndromes with ring sideroblasts (MDS-RS) as a separate entity with single lineage (MDS-RS-SLD) or multilineage (MDS-RS-MLD) dysplasia. The more recent International Consensus Classification (ICC) distinguishes between MDS with SF3B1 mutation (MDS-SF3B1) and MDS-RS without SF3B1 mutation; the latter is instead included under the category of MDS not otherwise specified. The current study includes 170 Mayo Clinic patients with WHO4R-defined MDS-RS, including MDS-RS-SLD (N=83) and MDS-RSMLD (N=87); a subset of 145 patients were also evaluable for the presence of SF3B1 and other mutations, including 126 with (87%) and 19 (13%) without SF3B1 mutation. Median overall survival for all 170 patients was 6.6 years with 5- and 10-year survival rates of 59% and 25%, respectively. A significant difference in overall survival was apparent between MDS-RS-MLD and MDS-RS-SLD (P<0.01) but not between MDS-RS with and without SF3B1 mutation (P=0.36). Multivariable analysis confirmed the independent prognostic contribution of MLD (hazard ratio=1.8, 95% confidence interval: 1.1-2.8; P=0.01) and also identified age (P<0.01), transfusion need at diagnosis (P<0.01), and abnormal karyotype (P<0.01), as additional risk factors; the impact from SF3B1 or other mutations was not significant. Leukemia-free survival was independently affected by abnormal karyotype (P<0.01), RUNX1 (P=0.02) and IDH1 (P=0.01) mutations, but not by MLD or SF3B1 mutation. Exclusion of patients not meeting ICC-criteria for MDS-SF3B1 did not change the observations on overall survival. MLD-based, as opposed to SF3B1 mutation-based, disease classification for MDS-RS might be prognostically more relevant.

Objectively measured activity is not associated with average pain intensity 1 week after surgery: A cross-sectional study.

Measures of physical activity and pain-related patient-reported outcomes are important components of patient recovery after surgery. However, little is known about their association in the early post-operative period. This study aims to increase this knowledge. Our primary objective was to determine the association between average pain intensity and activity (in steps) 1 week after surgery. Secondary objectives were the association of activity with other patient-reported outcomes, age, sex, comorbidities and body mass index. Data were obtained from the PROMPT sub-project of IMI-PainCare. Patients after breast and endometriosis-related surgery, sternotomy and total knee arthroplasty completed pain-related outcomes questionnaires and wore an ActiGraph activity-tracking device. We correlated steps with average pain intensity on post-operative days 6 and 7. Secondary analyses were done using correlations and t-tests. In 284 cases, there was no statistically significant correlation between steps and average pain intensity. In addition, none of the 28 secondary analyses showed a statistically significant result. Pain-related patient-reported outcome measures and physical activity are separate entities. Both should be measured after surgery to assess patient recovery and to identify treatment deficiencies. Measuring recovery is a multi-dimensional challenge. After surgery, clinicians need to be aware that neither pain intensity nor activity levels tell the whole story. Each can hint to problems and treatment requirements.

Piercing the corporate veil—the trust connection

Abstract The principle of separate legal entity which forms the basic foundation of company law provides for the company as a separate legal entity. This results in the formation of a veil, so to say, that protects the liability of the directors or other related companies from incurring liability. Under the Doctrine of Piercing the Corporate Veil, the said veil can be disregarded in certain circumstances. Historically, this principle has been restricted to companies incorporated under statute. However, recently, a High Court of India applied the doctrine to a Charitable Trust which is a non-corporate body. With Courts of India not providing any contours or sound reasoning towards the extension of the doctrine to non-corporate bodies, this article examines the application of the doctrine on charitable trusts, the flaws and problems that arise from such application and the possible solutions for the same while tracing evolved and developing jurisprudence surrounding the doctrine in taxation cases and trusts.

A holistic perspective on species delimitation outperforms all methods based on single data types in freshwater gastropods (Caenogastropoda: Hydrobiidae: Pseudamnicola)

Abstract Freshwater gastropods are one of the most species-rich and severely threatened animal groups in continental aquatic ecosystems. Unfortunately, understanding their species diversity, which is key to conservation, is often hampered by their small size, simple morphology, and restricted distribution. This is particularly the case for spring snails of the genus Pseudamnicola (family Hydrobiidae), a species-rich taxon across the Mediterranean region. Contrasting species diversities derived from molecular phylogenies and traditional taxonomy call for a holistic approach, in which molecular markers are used to identify putative taxonomic units that can then be validated morphologically. We integrated DNA sequence and morphometric data from 92 populations into a species delimitation framework to assess the taxonomic status of 25 nominal and 14 informally recognized species of Pseudamnicola across its geographical range. Although seven discovery methods delimited a varying number of putative species, taking an integrative approach generally improved species support over single datasets. The statistically favoured integrative scheme corroborated 30 of the 39 initial species as separate entities, whereas nine require taxonomic re-evaluation. Six species are described here formally. Pseudamnicola exemplifies the importance of considering multiple lines of evidence to evaluate species diversity in taxonomically complex groups, with newly developed approaches providing the needed toolbox.

Interconnected Smart Transactive Microgrids—A Survey on Trading, Energy Management Systems, and Optimisation Approaches

The deployment of isolated microgrids has witnessed exponential growth globally, especially in the light of prevailing challenges faced by many larger power grids. However, these isolated microgrids remain separate entities, thus limiting their potential to significantly impact and improve the stability, efficiency, and reliability of the broader electrical power system. Thus, to address this gap, the concept of interconnected smart transactive microgrids (ISTMGs) has arisen, facilitating the interconnection of these isolated microgrids, each with its unique attributes aimed at enhancing the performance of the broader power grid system. Furthermore, ISTMGs are expected to create more robust and resilient energy networks that enable innovative and efficient mechanisms for energy trading and sharing between individual microgrids and the centralized power grid. This paradigm shift has sparked a surge in research aimed at developing effective ISTMG networks and mechanisms. Thus, in this paper, we present a review of the current state-of-the-art in ISTMGs with a focus on energy trading, energy management systems (EMS), and optimization techniques for effective energy management in ISTMGs. We discuss various types of trading, architectures, platforms, and stakeholders involved in ISTMGs. We proceed to elucidate the suitable applications of EMS within such ISTMG frameworks, emphasizing its utility in various domains. This includes an examination of optimization tools and methodologies for deploying EMS in ISTMGs. Subsequently, we conduct an analysis of current techniques and their constraints, and delineate prospects for future research to advance the establishment and utilization of ISTMGs.

Study on clinical, histopathological and dermoscopic features of palmoplantar pustulosis and palmoplantar psoriasis with pustules

Background: Palmo-plantar pustulosis (PPP) and palmoplantar psoriasis with pustules (PPso)/Palmoplantar pustular psoriasis are entities that present with chronic cyclical eruptions of vesicles and pustules of palms and soles, which were initially considered to be similar but was defined as separate entities by the international psoriasis council in 2007. Individuals with PPP are at increased risk of psoriasis vulgaris, psoriatic arthritis, autoimmune thyroid disease and 90% of pustulosis patients can have psoriasis-like rash at some stage of the disease. Aim was to assess the clinical, histopathological and dermoscopic features of PPP and palmoplantar psoriasis with pustules. Methods: A cross sectional analysis of all patients who presented to us over 1 year with vesicles and/or pustules of hands and/or feet and were diagnosed with PPP and palmoplantar psoriasis with pustules/palmoplantar pustular psoriasis, both clinically and histologically, were done. The severity was analysed using palmoplantar pustulosis area severity index (PPPASI) and the clinical, histological and dermoscopic features were noted. Results: Twenty-four patients were categorized into 2 groups of 12 each, with a male predominance in both the groups. Majority (66.6%) of PPP belonged to the age group of 20-40 years whereas 83% of PPso belonged to &gt;40 years of age. Dermoscopic findings noted in both groups were translucent yellow areas, yellow/red-brown globules, dotted regularly arranged vessels, yellow crust and globules following dermatoglyphics. Conclusions: The study, though with limited sample size, highlights few clinical, histopathological and dermoscopic features which helps in differentiating the two groups.

Similarities in the Electrographic Patterns of Delayed Cerebral Infarction and Brain Death After Aneurysmal and Traumatic Subarachnoid Hemorrhage.

While subarachnoid hemorrhage is the second most common hemorrhagic stroke in epidemiologic studies, the recent DISCHARGE-1 trial has shown that in reality, three-quarters of focal brain damage after subarachnoid hemorrhage is ischemic. Two-fifths of these ischemic infarctions occur early and three-fifths are delayed. The vast majority are cortical infarcts whose pathomorphology corresponds to anemic infarcts. Therefore, we propose in this review that subarachnoid hemorrhage as an ischemic-hemorrhagic stroke is rather a third, separate entity in addition to purely ischemic or hemorrhagic strokes. Cumulative focal brain damage, determined by neuroimaging after the first 2weeks, is the strongest known predictor of patient outcome half a year after the initial hemorrhage. Because of the unique ability to implant neuromonitoring probes at the brain surface before stroke onset and to perform longitudinal MRI scans before and after stroke, delayed cerebral ischemia is currently the stroke variant in humans whose pathophysiological details are by far the best characterized. Optoelectrodes located directly over newly developing delayed infarcts have shown that, as mechanistic correlates of infarct development, spreading depolarizations trigger (1) spreading ischemia, (2) severe hypoxia, (3) persistent activity depression, and (4) transition from clustered spreading depolarizations to a negative ultraslow potential. Furthermore, traumatic brain injury and subarachnoid hemorrhage are the second and third most common etiologies of brain death during continued systemic circulation. Here, we use examples to illustrate that although the pathophysiological cascades associated with brain death are global, they closely resemble the local cascades associated with the development of delayed cerebral infarcts.

The Spemann-Mangold organizer discovery and society

This paper analyzes the influence of Hans Spemann and Hilde Mangold's discovery of the embryonic organizer on society outside the narrower confines of embryology. It begins by overviewing how in the 1920s–1930s, the organizer discovery fit well into the agenda of both right-wing and left-wing political camps, as it supported holistic theories of biological development that aligned with their ideological views. The paper then explores the organizer's influence on the formation and interdisciplinary discussions of the 1930s Cambridge Theoretical Biology Club. Club member C.H. Waddington's concept of the epigenetic landscape, inspired in part by Spemann and Mangold's work, went on to impact diverse fields including mathematics, psychology, anthropology, architecture, and art. Examples include mathematician René Thom's catastrophe landscapes and the field of ekistics (the science of human settlements). Spemann and Mangold's creation of an embryo chimera by combining tissues from different newt species also helped shape philosophers' and artists' understanding of the relationship between nature and technology as an integrated whole rather than separate entities. Additionally, Spemann's embryonic field concept helped influence field theories in other areas of science, and thinkers have pointed out metaphorical similarities between the organizer experiment and philosophical dialectics, film editing, or historical events. However, several factors likely limited the long-term societal impact of Spemann's holistic perspective, notably the rise of molecular biology and DNA-centric reductionist views of biology in the mid-late 20th century. While such reductionism still dominates public perceptions of biology, there seems to be a renewed openness to holistic perspectives reminiscent of Spemann's views.

Oral HPV-associated dysplasia: is koilocytic dysplasia a separate entity?

Oral epithelial dysplasia associated with high-risk HPV infection has received different names since its initial description, such as oral Bowenoid lesions, HPV-associated intraepithelial neoplasia, and oral koilocytic dysplasia. Some features, identified in more or less quantity in some of the descriptions, like apoptotic keratinocytes, karyorrhexis, and mitosoid figures, are intricately connected to viral transcriptional status and, consequently, viral load. Since the variety in terminology has introduced diagnostic confusion within medical and research communities, establishing a uniform and standardized approach to diagnosing HPV-oral epithelial dysplasia is crucial for accurate and early diagnoses and holds significant implications for patient outcomes, particularly in high-risk individuals.

Governing Ethical Gaps in Distributed AI Development

Good business practice often leads companies to subdivide into separate functional entities for operational efficiency and specialization. However, these kinds of divisions can generate significant ethical and perhaps even regulatory gaps when they occur in AI companies. In particular, one natural division for an AI company is into separate entities responsible for model development, testing, and cybersecurity (to maintain and protect data). In this paper, we argue that this division can lead to some ethical responsibilities always being “someone else’s job.” For concreteness, we consider the US National Institute of Standards and Technology’s AI Risk Management Framework (NIST AI RMF) as a guide to ethical obligations in a corporate context. We show that a common division of labor in AI development and deployment can lead to specific obligations for which no entity is responsible, even though they apply to the effort as a whole. We propose “Join Accountability Agreements”, a mechanism to ensure that ethical obligations do not slip through the cracks because of the way an effort is structured. We thus aim to highlight the significance of comprehensive examinations of and adaptable strategies for our ethical obligations when developing AI systems in a distributed manner.

Gestational trophoblastic disease a contemporary review of diagnostic and pathology. Current challenge and future directions for gynecologists and obstetricians

Gestational trophoblastic disease (GTD) is a heterogenous group of disorders assosiated with abnromal proliferation of trophoblast and their course is characterized by varying degrees of malignancy. WHO classified GTD into three categories: tumor-like lesions, molar pregnancies and gestational trophoblastic neoplasms.HM is characterized by abnormal proliferation of both syncytiotrophoblast and cytotrophoblast, edema of placental villi, with or without the presence of a fetus. Complete and partial moles have been classified as two separate disease entities, and their division depends on the genetic material they contain. The complete mole has a complete set of chromosomes coming only from paternal genome, while the partial mole is triploid and the genetic material transferred comes from the father and the mother. Post-molar gestational trophoblast neoplasia (GTN) is a clinical diagnosis based on the observation of a persistent increase or persistently high hCG concentration after evacuation of the mole, requiring evaluation and treatment. Invasive hydatidiform mole, together with choriocarcinoma and placental tumor, belong to gestational trophoblast neoplasia. Currently, research has shown that short tandem repeat (STR) genotyping is the gold standard for making the correct diagnosis and this test should be performed if possible. GTD diseases originate from both syncytiotrophoblast and cytotrophoblast tissues and as a result of which they produce an extremely sensitive marker -human chorionic gonadotropin. The facts stated above and significant sensitivity to chemotherapy mean that the average cure rate for this disease currently exceeds 90%. Although the main treatment of gestational trophoblast neoplasia involves the use of cytostatics in cases with worse prognosis, i.e. those with a higher risk, surgery turns out to be an invaluable treatment method.

Climate and biodiversity change constrain the flow of cultural ecosystem services to people: A case study modeling birding across Africa under future climate scenarios

Global change is currently impacting ecosystems and their contributions to people (i.e. ecosystem services). These impacts have consequences for societies and human well-being, especially in Africa. Historically, efforts have focused on assessing global change from a social or biophysical perspective, treating them as separate entities. Yet, our understanding of impacts to social-ecological systems remains limited, particularly in the Global South, due to a lack of data, tools, and approaches accounting for social and ecological aspects of ecosystem services. This is especially relevant for cultural ecosystem services as they are less tangible. We use a simple indicator and important provider of a multitude of cultural ecosystem services, birding, to understand how climate, biodiversity, and land use change will impact cultural ecosystem services across Africa. We explore how emerging tools and data can overcome limitations in mapping and modeling cultural ecosystem services, particularly in analyzing human preferences and behavior at large spatiotemporal scales and in data-poor regions. Leveraging crowdsourced data from eBird and using machine learning techniques we map and model recreational birding to assess the underlying social-ecological relationships and the impact of future climate and environmental change. We show that bird species richness, protected areas, accessibility, and max temperature contribute most to birding suitability across the continent. Further, we show spatial shifts in the suitability of birding under three future climate scenarios (SSP126, 370, and 585). Models suggest climate and biodiversity change will increasingly constrain the flow of birding related cultural ecosystem services across Africa. This has implications for human-nature interactions, development of countries, management of protected areas, and overall human well-being in the future. More generally, we highlight opportunities for crowdsourced datasets and machine learning to integrate non-material ecosystem services in models and thus, enhance the understanding of future impacts to ecosystem services and human well-being.

Neuronal travelling waves explain rotational dynamics in experimental datasets and modelling

Spatiotemporal properties of neuronal population activity in cortical motor areas have been subjects of experimental and theoretical investigations, generating numerous interpretations regarding mechanisms for preparing and executing limb movements. Two competing models, representational and dynamical, strive to explain the relationship between movement parameters and neuronal activity. A dynamical model uses the jPCA method that holistically characterizes oscillatory activity in neuron populations by maximizing the data rotational dynamics. Different rotational dynamics interpretations revealed by the jPCA approach have been proposed. Yet, the nature of such dynamics remains poorly understood. We comprehensively analyzed several neuronal-population datasets and found rotational dynamics consistently accounted for by a traveling wave pattern. For quantifying rotation strength, we developed a complex-valued measure, the gyration number. Additionally, we identified parameters influencing rotation extent in the data. Our findings suggest that rotational dynamics and traveling waves are typically the same phenomena, so reevaluation of the previous interpretations where they were considered separate entities is needed.

Quality of Life of Oligometastatic and Polymetastatic Head and Neck Squamous Cell Carcinoma Patients.

Evidence suggests that distant metastasis in head and neck squamous cell carcinoma is a spectrum of disease. Previous studies show that oligometastasis has favorable survival compared with polymetastasis. The quality of life of patients with oligometastasis remains unknown. To further solidify the position of oligometastasis as a separate entity, we hypothesized that oligometastatic patients experience better quality of life than polymetastatic patients. Patients with distant metastasis were stratified into three groups: oligometastasis (≤3 metastatic foci in ≤2 anatomic sites), explosive metastasis (≥4 metastatic foci at one anatomic site), and explosive-disseminating metastasis (spread to ≥3 anatomic sites). Quality of life was assessed every 2 months post distant metastasis diagnosis. Between January 1, 2016, and December 31, 2021, a total of 161 patients with distant metastasis were identified, with a total of 397 measurements. In this group, 57 (35.4%) patients had oligometastasis, 35 (21.7%) patients had explosive metastasis, and 69 (42.9%) patients had explosive-disseminating metastasis. Their median post-distant metastasis survivals were 8.5 months, 3.2 months, and 3.2 months respectively (p < 0.001). A significantly better overall quality of life was observed in the oligometastasis group compared with the polymetastatic groups (+0.75 out of 7, p < 0.05). Furthermore, oligometastatic patients performed better in the subdomains of "physical functioning," "fatigue," and "pain." Results from this study underscore that subgroups exist regarding quality of life and survival within distant metastasis, with polymetastatic patients performing worse than oligometastatic patients. This highlights the significance of tailored interventions that consider the unique challenges faced by each metastatic group of patients. 3, retrospective cohort study Laryngoscope, 134:3170-3176, 2024.

Galli-Galli Disease: A Comprehensive Literature Review.

Galli-Galli disease (GGD) is a rare genodermatosis that exhibits autosomal dominant inheritance with variable penetrance. GGD typically manifests with erythematous macules, papules, and reticulate hyperpigmentation in flexural areas. A distinct atypical variant exists, which features brown macules predominantly on the trunk, lower limbs, and extremities, with a notable absence of the hallmark reticulated hyperpigmentation in flexural areas. This review includes a detailed literature search and examines cases since GGD's first description in 1982. It aims to synthesize the current knowledge on GGD, covering its etiology, clinical presentation, histopathology, diagnosis, and treatment. A significant aspect of this review is the exploration of the genetic, histopathological, and clinical parallels between GGD and Dowling-Degos disease (DDD), which is another rare autosomal dominant genodermatosis, particularly focusing on their shared mutations in the KRT5 and POGLUT1 genes. This supports the hypothesis that GGD and DDD may be different phenotypic expressions of the same pathological condition, although they have traditionally been recognized as separate entities, with suprabasal acantholysis being a distinctive feature of GGD. Lastly, this review discusses the existing treatment approaches, underscoring the absence of established guidelines and the limited effectiveness of various treatments.

Primary sclerosing cholangitis and inflammatory bowel disease: a complicated yet unique relationship.

Primary sclerosing cholangitis (PSC) is a rare liver disorder characterized by biliary ducts inflammation, fibrosis and consequently chronic cholestasis, which progressively lead to liver cirrhosis. The main feature of PSC is the frequent association with inflammatory bowel disease (IBD), with an estimated prevalence of around 70% of the cases. This strong relationship seems due to the presence of shared pathogenetic mechanisms, which seem to involve the intestinal barrier function, the human gut microbiota and the immune innated and adaptative response to antigens derived from the bowel. Of relevance, PSC-IBD have specific clinical and pathological features that differ from PSC and IBD as separate entities, explaining the diversity in outcomes among these categories, and therefore the distinct clinical management that is required. The aim of this review is to present recent data regarding the epidemiology, pathobiology and clinical features of PSC-IBD.

WUTSUP-02-II-Neo-Dis-Tis: Investigating the efficacy and safety of neoadjuvant tislelizumab plus disitamab vedotin with adjuvant tislelizumab in upper urinary tract carcinoma—A phase II multi-center study.

TPS718 Background: Upper tract urothelial carcinoma (UTUC) and urothelial bladder cancer (UBC) are frequently referred to as “disparate twins” despite their common tissue origin. They exhibit varying biological behaviors, prognostic outcomes, and responses to treatment. It is crucial to conduct dedicated clinical trials for UTUC as a separate entity rather than relying solely on UBC study results, giving that UTUC lags in evidence quantity and quality compared to UBC. Despite the superior outcomes of neoadjuvant treatment over adjuvant treatment in UBC trials, the currently available evidence for neoadjuvant therapy of UTUC remains limited in quantity and diversity, as the largest trial, POUT, is focused on adjuvant therapy. Additionally, the limited number of neoadjuvant trials for UTUC primarily utilize chemotherapy-based regimens, with little investigation into combination therapies. Of note, UTUC patients frequently have impaired renal functions, making a chemotherapy-independent approach a desirable alternative. On the other hand, given the short duration of neoadjuvant therapy, a combination therapy strategy appears to be necessary, especially with the increasing interest in immune therapy maintenance after surgery. Tislelizumab has demonstrated efficacy in patients with advanced or metastatic urothelial carcinoma. Disitamab Vedotin, a HER2-targeting antibody-drug conjugate (ADC), has demonstrated robust clinical efficacy in metastatic urothelial carcinoma patients with HER2 2+ or 3+ expression. Disitamab Vedotin in combination with PD-1 immunotherapy has shown remarkable results in locally advanced or metastatic urothelial carcinoma, regardless of HER2 expression, indicative of a synergistic effect between ADC and PD-1 immunotherapy. In this study, we aim to conduct a prospective phase II trial to investigate the efficacy and safety of neoadjuvant tislelizumab plus Disitamab Vedotin followed by adjuvant tislelizumab in patients with high-risk UTUC. Methods: This multi-center phase II trial aims to enroll 45 patients with histologically confirmed UTUC at clinical stage cT2-4N0M0 or cT1-4N1-2M0. Neoadjuvant therapy includes 4 cycles of Tislelizumab (200mg for each 3-week cycle) in combination with Disitamab Vedotin (2.0mg/kg for each 3-week cycle). Radical nephroureterectomy (including bladder cuff resection and regional lymph node dissection if indicated) will be performed if there is no obvious contraindication within 3-6 weeks after the final neoadjuvant therapy administration. Postoperative adjuvant treatment with 8 cycles of tislelizumab will be provided. The primary endpoint is pathological complete response rate. Secondary endpoints include overall survival, local recurrence free survival, distant metastasis free survival, FACT–G. Clinical trial information: ChiCTR2300067836 .

Comparative study of the peroneus tertius muscle in pigs based on the origin, course, insertion and innervation.

That the peroneus tertius muscle (PT) is a separate entity has been debated. PT has been reported to be part of the extensor digitorum longus muscle, part of the extensor digitorum brevis, or a separate muscle. While pigs have a PT as well as primates, there are no reports of its association with the extensor digitorum longus muscle or extensor digitorum brevis. In this study, we used gross dissection and Sihler's staining to determine the origin, course, insertion, and innervation of the pig PT. The PT and extensor digitorum longus muscles jointly originated from the femur and ran between the tibialis cranialis and peroneus longus muscles. The PT was inserted at the retinaculum of the metatarsal extensors, tarsal bone, and second metatarsal bone. The branches of the common fibular nerve to the extensor digitorum longus muscle were distributed to the PT. The innervations suggest that the PT and extensor digitorum longus muscles of the pig were derived from the same muscle mass during development but were named separately due to differences in their morphology. Furthermore, morphological features suggest that pig PT and human PT are probably different muscles.

P397 Distinct blood protein profiles associated with ileal and colonic ulcers in Crohn’s disease

Abstract Background Ileal and colonic Crohn’s disease (CD) are nowadays considered as separate entities. Studies are needed to better characterise the biological specificities of these subphenotypes. In fine, this research should offer opportunities for the development of personalised medicine. Methods By combining different technologies (proximity extension assay, selected reaction monitoring and high-sensitivity turbidimetric immunoassay (hsCRP)), 207 serum proteins were measured in CD patients presenting no endoscopic lesions (endoscopic remission) (n=23), isolated ileal ulcers (n=17) or isolated colonic ulcers (n=16) (Table 1). To compare the endoscopic activity between the ileum and colon, and in order to obtain an assessment of the overall lesion burden, we used the Crohn’s disease endoscopic index (CDEIS) without dividing its total score (sum of each gut segment) by the number of inspected segments. The data analysis was conducted using Wilcoxon-Mann-Whitney test and area under the receiver operating characteristics curve (AUROC). The AUROC were compared using the bootstrap test (2000 replications). Results The median of the total CDEIS was higher in CD patients with isolated colonic ulcers than those with isolated ileal ulcers (23.1 vs 8.0) (Table 1). When compared to endoscopic remission, the presence of isolated ileal ulcers and isolated colonic ulcers were specifically associated with the level of 6 and 18 serum proteins, respectively: (high: JUN, CNTNAP2; low: FCRL6, LTA, CLEC4A, NTF4) (Figure 1A); (high: hsCRP, IL6, APCS, CFB, MBL2, IL7, IL17A, CCL19, CXCL10, CSF3, IL10, CLEC4G, MMP12, VEGFA; low: CLEC3B, GSN, TNFSF12, TPSAB1) (Figure 1B). No protein was associated with both isolated ileal ulcers and isolated colonic ulcers (Figure 1). All CD patients in endoscopic remission showed a normal level of hsCRP (&amp;lt;5 mg.L-1). Compared to CD patients in endoscopic remission, CD patients with isolated colonic ulcers showed an increased median level of hsCRP (1.3 vs 5.9 mg.L-1, p-value=0.0045) and this was not the case for CD patients presenting isolated ileal ulcers (1.3 vs 2.2 mg.L-1, p-value=0.13). hsCRP detected ileal and colonic ulcers with an AUROC of 0.64 (p-value=0.07) and 0.77 (p-value=0.001), respectively. When compared to hsCRP (AUROC), the best marker pairs for detecting ileal or colonic ulcers were respectively CLEC4A×LTA (0.82 vs 0.64, p-value=0.06) or hsCRP×CSF3 (0.85 vs 0.77, p-value =0.02). Conclusion In CD patients, ileal and colonic ulcers were associated with distinct systemic responses. hsCRP showed a better capacity to detect patients with colonic than ileal ulcers. Some markers might help to detect ileal ulcers or to improve the ability of CRP for detecting colonic ulcers.