pinecone/core-2020-05-10-deduplication huggingface dataset:
Dynamics of a headwater system and peatland under current conditions and with climate change

Interactions between headwater aquifers and peatlands have received limited scientific attention. Hydrological stresses, including those related to climate change, may adversely impact these interactions. In this study, the dynamics of a southern Québec headwater system where a peatland is present is simulated under current conditions and with climate change. The model is calibrated in steady state on field-measured data and provides satisfactory results for transient-state conditions. Under current conditions, simulations confirm that the peatland is fed by the fractured bedrock aquifer year-round and provides continuous baseflow to its outlets. Climate change is simulated through its impact on groundwater recharge. Predicted precipitation and temperature data from a suite of regional climate model scenarios provide a net precipitation variation range from +10% to −30% for the 2041–2070 horizon. Calibrated recharge is modified within this range to perform a sensitivity analysis of the headwater model to recharge variations (+10%, −15% and −30%). Total contribution from the aquifer to rivers and streams varies from +14% to −44% of the baseline for +10% to −30% recharge changes from spring 2010 data, for example. With higher recharge, the peatland receives more groundwater, which could significantly change its vegetation pattern and eventually ecosystem functions. For a −30% recharge, the peatland becomes perched above the aquifer during the summer, fall and winter. Recharge reductions also induce sharp declines in groundwater levels and drying streams
Critical assessment and validation of a time-integrating fluvial suspended sediment sampler.

Delivery of fine sediment to fluvial systems is of considerable concern given the physical and ecological impacts of elevated levels in drainage networks. Although it is possible to measure the transfer of fine sediment at high frequency by using a range of surrogate and automated technologies, the demands for assessing sediment flux and sediment properties at multiple spatially distributed locations across catchments can often not be met using established sampling techniques. The time-integrated mass-flux sampler (TIMS) has the potential to bridge this gap and further our understanding of fine sediment delivery in fluvial systems. However, these devices have undergone limited testing in the field. The aim of this paper was to provide a critical validation of TIMS as a technique for assessing fluvial fine sediment transfer. Fine sediment flux and sediment properties were assessed over 2 years with individual sampling periods of approximately 30 days. Underestimation of sediment flux ranged between 66% and 99% demonstrating that TIMS is unsuitable for assessing absolute sediment loads. However, assessment of relative efficiency showed that six of seven samplers produced statistically strong relationships with the reference sediment load (P < 0.05). Aggregated data from all sites produced a highly significant relationship between reference and TIMS loads (R2 = 0.80; P < 0.001) demonstrating TIMS may be suitable for characterizing patterns of suspended sediment transfer. Testing also illustrated a consistency in sediment properties between multiple samplers in the same channel cross section. TIMS offers a useful means of assessing spatial and temporal patterns of fine sediment transfer across catchments where expensive monitoring frameworks cannot be commissioned
Intestinal barrier dysfunction in inflammatory bowel diseases

The etiology of human inflammatory bowel diseases (IBDs) is believed to involve inappropriate host responses to the complex commensal microbial flora in the gut, although an altered commensal flora is not completely excluded. A multifunctional cellular and secreted barrier separates the microbial flora from host tissues. Altered function of this barrier remains a major largely unexplored pathway to IBD. Although there is evidence of barrier dysfunction in IBD, it remains unclear whether this is a primary contributor to disease or a consequence of mucosal inflammation. Recent evidence from animal models demonstrating that genetic defects restricted to the epithelium can initiate intestinal inflammation in the presence of normal underlying immunity has refocused attention on epithelial dysfunction in IBD. We review the components of the secreted and cellular barrier, their regulation, including interactions with underlying innate and adaptive immunity, evidence from animal models of the barrier\u27s role in preventing intestinal inflammation, and evidence of barrier dysfunction in both Crohn\u27s disease and ulcerative colitis. (Inflamm Bowel Dis 2008
Evidence for a role of epithelial mesenchymal transition during pathogenesis of fistulae in Crohn's disease

BACKGROUND: The pathogenesis of fistulae in Crohn's disease (CD) patients is barely understood. We recently showed that more than two-thirds of CD fistulae are covered with flat, mesenchymal-like cells (transitional cells [TC]) forming a patchy basement membrane. Epithelial-to-mesenchymal transition (EMT) is a process of reprogramming epithelial cells, allowing them to migrate more effectively and giving epithelial cells an "invasive" potential. EMT has been suggested to be crucial in fibrosis found in different tissues and diseases. We therefore investigated whether EMT could be involved in the pathogenesis of fistulae formation in CD. METHODS: In all, 18 perianal fistulae, 2 enteroenteric, and 1 enterovesical fistulae from 17 CD patients were analyzed. In addition 2 perianal fistulae of non-CD patients were studied. Hematoxylin and eosin staining, immunohistochemistry for the expression of cytokeratins 8 and 20, beta6-integrin, E-cadherin, beta-catenin, vimentin, and TGF-beta1 and 2 were performed according to standard techniques. RESULTS: The TC covering perianal or enteroenteric fistulae were strongly positive for cytokeratins 8 and 20 but negative for vimentin, indicating their epithelial origin. beta6-Integrin and TGF-beta had the highest staining intensities in the transitional zone between the epithelium and the TC. Expression of junctional proteins such as E-cadherin was reduced in TC as compared to regular fistulae epithelium. In addition, a translocation of beta-catenin from the membrane to the cytoplasm was observed. CONCLUSIONS: Our data for the first time indicate an expression pattern of epithelial and mesenchymal markers in TC associated with fistulae formation that is characteristic for EMT. Studying the pathways of EMT during intestinal fistulae formation may help to develop new therapeutic strategies
Gene expression profiles of mucosal fibroblasts from strictured and nonstrictured areas of patients with Crohn's disease

Background: A frequent complication of Crohn's disease (CD) is the formation of strictures and stenoses. Strictures are characterized by a fibrosis of the bowel wall, induced by abnormal wound healing. Functional changes of colonic lamina propria fibroblasts (CLPF) reflected by increased proliferation and collagen synthesis, increased contractility or reduced migratory potential, indicate a change of the phenotype. We aimed to investigate differences in gene expression profiles between CLPF isolated from normal, inflamed and strictured areas of CD patients.\ud
Methods: We applied two methods of gene expression analysis, subtractive hybridisation and Affimetrix(R) microarrays to find differences in mRNA expression patterns. Findings were verified by dot blot analysis.\ud
Results: Using subtractive screening and dot blot analysis 74 clones could be confirmed to be differentially expressed in CD CLPF from nonstrictured areas compared to control CLPF. Fibronectin (transcript variant 1, NM_002026) could be confirmed as being upregulated in CD with a ratio of 143. Collagen (type I, NM_000089) was upregulated in CD with a ratio of 17.41 clones could be confirmed as differentially expressed in CD CLPF derived from strictures compared to control CLPF. Five clones were identified as chitinase 3-like 1 (cartilage glycoprotein-39) and confirmed with dot blot with a ratio of 2.1.In an independent approach, microarray analysis showed upregulation of chitinase 3-like 1 (signal log ratio 1.9) in CD CLPF from strictures compared to control CLPF thus confirming subtractive hybridization.Conclusions: In the light of the current literature a number of interesting candidates resulted from the multiplicity of identified genes. In regard to the functional changes of CLPF during stenosis and other dysfunctions some proteins might represent a therapeutic target
Circulating levels of chemerin and adiponectin are higher in ulcerative colitis and chemerin is elevated in Crohn's disease

BACKGROUND:: Chemerin is an adipokine that stimulates chemotaxis of cells of the innate immune system. Inflammatory bowel disease (IBD) is linked to an impaired immune response and, therefore, we hypothesized that systemic chemerin may be altered in IBD patients. METHODS:: Serum was collected from patients with Crohn's disease (CD, 230 patients), ulcerative colitis (UC, 80 patients), and healthy controls (HC, 80 probands). Chemerin and adiponectin, which has already been measured in the serum of similar cohorts by others, were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS:: Chemerin was elevated in IBD compared to HC and was higher in male CD than UC patients. Female and male CD patients had lower adiponectin levels compared to UC, and adiponectin was lower in female CD patients compared to female HC. Adiponectin tended to be higher in female and male UC patients compared to HC and this difference became significant in the whole study group. Correlations with disease activity were only found in males. Here, chemerin was higher in CD patients on remission but was reduced in UC with nonactive disease. Adiponectin was higher in UC with inactive disease. Treatment with corticosteroids was linked to elevated adiponectin in male CD patients and higher chemerin in female UC patients. Unlike adiponectin, which was elevated in female serum in all cohorts, chemerin was only higher in female UC patients. CONCLUSIONS:: These findings further indicate potential regulatory functions of adipokines in intestinal inflammation that are partly gender-dependent and that may even be associated with the distinct immunopathogenesis of UC and CD. (Inflamm Bowel Dis 2009;)
Capsule endoscopy in inflammatory bowel disease type unclassified and indeterminate colitis serologically negative

BACKGROUND:
The value of capsule endoscopy in the setting of inflammatory bowel disease type unclassified (IBDU) and indeterminate colitis (IC) remains obscure. The aim was to evaluate the clinical impact of capsule endoscopy on IBDU/IC patients with negative serology.
METHODS:
Eighteen patients with long-standing IBDU (n = 14) and IC (n = 4) were enrolled to undergo a capsule endoscopy and then followed prospectively. Lesions considered diagnostic of Crohn's disease (CD) were 4 or more erosions/ulcers and/or a stricture. The median follow-up time after capsule endoscopy was 32 ± 11 months (23-54 months).
RESULTS:
Total enteroscopy was possible in all patients. In 2 patients the examination was normal (Group 1). In 9 patients subtle findings were observed (Group 2): focal villi denudation (n = 1) and fewer than 4 erosions/ulcers (n = 8). In 7 patients, 4 or more erosions/ulcers were detected (Group 3), leading to a diagnosis of CD. However, their treatment was not reassessed on the basis of the capsule findings. Until now, a definitive diagnosis has been achieved in 2 additional patients: 1 from Group 1 (ulcerative colitis) and another patient from Group 2 (CD), who began infliximab infusions. Nine patients remained indeterminate at follow-up.
CONCLUSIONS:
Although capsule endoscopy enabled the diagnosis of CD in 7 patients, in none of them was the clinical management changed. Moreover, a change in therapy due to a diagnosis of CD was made for only 1 patient, who presented nonspecific findings. Our results suggest that capsule findings are not helpful in the work-up of these patient
Risk factors for metabolic bone disease in Crohn's disease patients

Background: The aim was to evaluate the presence of metabolic bone disease (MBD) in patients with Crohn’s disease (CD) and to identify potential etiologic factors. Methods: The case–control study included 99 patients with CD and 56 controls with a similar age and gender distribution. Both
groups had dual-energy x-ray absorptionmetry and a nutritional evaluation. Single nucleotide polymorphisms at the IL1, TNF-a,
LTa, and IL-6 genes were analyzed in patients only. Statistical analysis was performed using SPSS software. Results: The prevalence of MBD was significantly higher in
patients (P ¼ 0.006). CD patients with osteoporosis were older (P < 0.005), small bowel involvement and surgical resections were more frequent (P < 0.005), they more often exhibited a penetrating or stricturing phenotype (P < 0.05), duration of disease
over 15 years (P < 0.005), and body mass index (BMI) under 18.5 kg/m2 (P < 0.01) were more often found. No association was found with steroid use. Patients with a Z-score <  2.0 more frequently had chronic active disease (P < 0.05). With regard to diet, low vitamin K intake was more frequent (P ¼ 0.03) and intake of total, monounsaturated, and polyunsaturated fat was higher in patients with Z-score <  2.0 (P < 0.05). With respect to genetics, carriage of the polymorphic allele for LTa252 A/G was associated with a higher risk of osteoporosis (P ¼ 0.02). Regression analysis showed that age over 40 years, chronic active
disease, and previous colonic resections were independently associated with the risk of developing MBD. Conclusions: The prevalence of MBD was significantly higher
in CD patients. Besides the usual risk factors, we observed that factors related to chronic active and long-lasting disease increased the risk of MBD
NLRP3 inflammasome plays a key role in the regulation of intestinal homeostasis.

BACKGROUND:: Attenuated innate immune responses to the intestinal microbiota have been linked to the pathogenesis of Crohn's disease (CD). Recent genetic studies have revealed that hypofunctional mutations of NLRP3, a member of the NOD-like receptor (NLR) superfamily, are associated with an increased risk of developing CD. NLRP3 is a key component of the inflammasome, an intracellular danger sensor of the innate immune system. When activated, the inflammasome triggers caspase-1-dependent processing of inflammatory mediators, such as IL-1β and IL-18. METHODS:: In the current study we sought to assess the role of the NLRP3 inflammasome in the maintenance of intestinal homeostasis through its regulation of innate protective processes. To investigate this role, Nlrp3(-/-) and wildtype mice were assessed in the dextran sulfate sodium and 2,4,6-trinitrobenzenesulfonic acid models of experimental colitis. RESULTS:: Nlrp3(-/-) mice were found to be more susceptible to experimental colitis, an observation that was associated with reduced IL-1β, reduced antiinflammatory cytokine IL-10, and reduced protective growth factor TGF-β. Macrophages isolated from Nlrp3(-/-) mice failed to respond to bacterial muramyl dipeptide. Furthermore, Nlrp3-deficient neutrophils exhibited reduced chemotaxis and enhanced spontaneous apoptosis, but no change in oxidative burst. Lastly, Nlrp3(-/-) mice displayed altered colonic β-defensin expression, reduced colonic antimicrobial secretions, and a unique intestinal microbiota. CONCLUSIONS:: Our data confirm an essential role for the NLRP3 inflammasome in the regulation of intestinal homeostasis and provide biological insight into disease mechanisms associated with increased risk of CD in individuals with NLRP3 mutations. (Inflamm Bowel Dis 2010)
Development of the Crohn's disease digestive damage score, the Lémann score.

Crohn's disease (CD) is a chronic progressive destructive disease. Currently available instruments measure disease activity at a specific point in time. An instrument to measure cumulative structural damage to the bowel, which may predict long-term disability, is needed. The aim of this article is to outline the methods to develop an instrument that can measure cumulative bowel damage. The project is being conducted by the International Program to develop New Indexes in Crohn's disease (IPNIC) group. This instrument, called the Crohn's Disease Digestive Damage Score (the Lémann score), should take into account damage location, severity, extent, progression, and reversibility, as measured by diagnostic imaging modalities and the history of surgical resection. It should not be "diagnostic modality driven": for each lesion and location, a modality appropriate for the anatomic site (for example: computed tomography or magnetic resonance imaging enterography, and colonoscopy) will be used. A total of 24 centers from 15 countries will be involved in a cross-sectional study, which will include up to 240 patients with stratification according to disease location and duration. At least 120 additional patients will be included in the study to validate the score. The Lémann score is expected to be able to portray a patient's disease course on a double-axis graph, with time as the x-axis, bowel damage severity as the y-axis, and the slope of the line connecting data points as a measure of disease progression. This instrument could be used to assess the effect of various medical therapies on the progression of bowel damage. (Inflamm Bowel Dis 2011)
DNA Methylation of Colon Mucosa in Ulcerative Colitis Patients: Correlation with Inflammatory Status

Background: Although DNA methylation of colonic mucosa in ulcerative colitis (UC) has been suggested, the majority of published reports indicate the correlation between methylation of colon mucosa and occurrence of UC-related dysplasia or cancer without considering the mucosal inflammatory status. The aim of this study was to verify whether mucosal inflammation-specific DNA methylation occurs in the colon of UC. 

Methods: Of 15 gene loci initially screened, six loci (ABCB1, CDH1. ESR1, GDNF, HPP1, and MYOD1) methylated in colon mucosa of UC were analyzed according to inflammatory status using samples from 28 surgically resected UC patients. 

Results: Four of six regions (CDH1, GDNF, HPP1, and MYOD1) were more highly methylated in the active inflamed mucosa than in the quiescent mucosa in each UC patient (P = 0.003, 0.0002, 0.02, and 0.048, respectively). In addition, when the methylation status of all samples taken from examined patients was stratified according to inflammatory status, methylation of CDHI and GDNF loci was significantly higher in active inflamed mucosa than in quiescent mucosa (P = 0.045 and 0.002, respectively). Multiple linear regression analysis revealed that active inflammation was an independent factor of methylation for CDHI and GDNF. DNA methyltransferase 1 and 3b were highly expressed in colon epithelial cells with active mucosa] inflammation, suggesting their involvement in inflammation-dependent methylation. 

Conclusions: Methylation in colonic mucosa of UC was correlated with mucosal inflammatory status, suggesting the involvement of methylation due to chronic active inflammation in UC carcinogenesis
Inflammatory Bowel Disease in Primary Sclerosing Cholangitis: Clinical Characteristics in Liver Transplanted and Non-Transplanted Patients

List of papers. The papers are removed from the thesis due to publisher restrictions.

Paper I Jørgensen KK, Grzyb K, Lundin KEA, Clausen OPF, Aamodt G, Schrumpf E, Vatn MH, Boberg KM. Inflammatory Bowel Disease in Patients with Primary Sclerosing Cholangitis: Clinical Characterization in Liver Transplanted and Nontransplanted Patients. Inflamm Bowel Dis 2012;3:536-545 <a href="http://dx.doi.org/10.1002/ibd.21699">doi:10.1002/ibd.21699</a>

Paper II Jørgensen KK, Lindström L, Cvancarova M, Castedal M, Friman S, Schrumpf E, Foss A, Isoniemi H, Nordin A, Holte K, Rasmussen A, Bergquist A, Vatn MH, Boberg KM. Colorectal Neoplasia in Patients with Primary Sclerosing Cholangitis undergoing Liver Transplantation: a Nordic Multicenter Study. Scand J Gastroenterol 2012;47:1021-1029 <a href="http://dx.doi.org/10.3109/00365521.2012.685754">doi:10.3109/00365521.2012.685754</a>

Paper III Jørgensen KK, Lindström L, Cvancarova M, Karlsen TH, Castedal M, Friman S, Schrumpf E, Foss A, Isoniemi H , Nordin A, Holte K, Rasmussen A, Bergquist A, Vatn MH, Boberg KM. Immunosuppression after liver transplantation for primary sclerosing cholangitis influences activity of inflammatory bowel disease. Clin Gastroenterol Hepatol 2013;11:517-523. <a href="http://dx.doi.org/10.1016/j.cgh.2012.12.027">doi:10.1016/j.cgh.2012.12.027</a
Computed tomography enterography findings correlate with tissue inflammation, not fibrosis in resected small bowel Crohn's disease

Background:  It has become commonplace to categorize small intestinal Crohn's disease (CD) as “active” vs. “inactive” or “inflammatory” vs. “fibrotic” based on computed tomography enterography (CTE) findings. Data on histologic correlates of CTE findings are lacking. We aimed to compare CTE findings with histology from surgically resected specimens. We tested the hypothesis that CTE findings can distinguish tissue inflammation from fibrosis.    Methods:  Patients who underwent CTE within 3 months before intestinal resection for CD were retrospectively studied. Radiologists blinded to history and histology scored findings on CTE. Pathologists blinded to history and imaging scored resected histology. We compared histology with CTE findings and radiologists assessment of whether the stricture was likely “active” or “inactive.”    Results:  In all, 22 patients met inclusion criteria. Inflammatory CTE findings correlated with histologic inflammation (rho = 0.52). Strictures believed to be “active” on CTE were more inflamed at histology ( P  = 0.0002). Strictures lacking inflammatory findings on CTE or considered “inactive” were not associated with greater histologic fibrosis or significant histologic inflammation. Upstream dilation was associated with greater tissue fibrosis in univariate ( P  = 0.014) but not in multivariate analysis ( P  = 0.53). Overall, histologic fibrosis correlated best with histologic inflammation (rho = 0.52). Strictures on CTE with the most active disease activity also had the most fibrosis on histology.    Conclusions:  CTE findings of mesenteric hypervascularity, mucosal hyperenhancement, and mesenteric fat stranding predict tissue inflammation. However, small bowel stricture without CTE findings of inflammation does not predict the presence of tissue fibrosis. Therefore, caution should be used when using CTE criteria to predict the presence of scar tissue. (Inflamm Bowel Dis 2011;