Search results for: Jan Willem T. Dekker
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 11

Search results for: Jan Willem T. Dekker

11 Time-Interval between Rectal Cancer Surgery and Reintervention for Anastomotic Leakage and the Effects of a Defunctioning Stoma: A Dutch Population-Based Study

Authors: Anne-Loes K. Warps, Rob A. E. M. Tollenaar, Pieter J. Tanis, Jan Willem T. Dekker

Abstract:

Anastomotic leakage after colorectal cancer surgery remains a severe complication. Early diagnosis and treatment are essential to prevent further adverse outcomes. In the literature, it has been suggested that earlier reintervention is associated with better survival, but anastomotic leakage can occur with a highly variable time interval to index surgery. This study aims to evaluate the time-interval between rectal cancer resection with primary anastomosis creation and reoperation, in relation to short-term outcomes, stratified for the use of a defunctioning stoma. Methods: Data of all primary rectal cancer patients that underwent elective resection with primary anastomosis during 2013-2019 were extracted from the Dutch ColoRectal Audit. Analyses were stratified for defunctioning stoma. Anastomotic leakage was defined as a defect of the intestinal wall or abscess at the site of the colorectal anastomosis for which a reintervention was required within 30 days. Primary outcomes were new stoma construction, mortality, ICU admission, prolonged hospital stay and readmission. The association between time to reoperation and outcome was evaluated in three ways: Per 2 days, before versus on or after postoperative day 5 and during primary versus readmission. Results: In total 10,772 rectal cancer patients underwent resection with primary anastomosis. A defunctioning stoma was made in 46.6% of patients. These patients had a lower anastomotic leakage rate (8.2% vs. 11.6%, p < 0.001) and less often underwent a reoperation (45.3% vs. 88.7%, p < 0.001). Early reoperations (< 5 days) had the highest complication and mortality rate. Thereafter the distribution of adverse outcomes was more spread over the 30-day postoperative period for patients with a defunctioning stoma. Median time-interval from primary resection to reoperation for defunctioning stoma patients was 7 days (IQR 4-14) versus 5 days (IQR 3-13 days) for no-defunctioning stoma patients. The mortality rate after primary resection and reoperation were comparable (resp. for defunctioning vs. no-defunctioning stoma 1.0% vs. 0.7%, P=0.106 and 5.0% vs. 2.3%, P=0.107). Conclusion: This study demonstrated that early reinterventions after anastomotic leakage are associated with worse outcomes (i.e. mortality). Maybe the combination of a physiological dip in the cellular immune response and release of cytokines following surgery, as well as a release of endotoxins caused by the bacteremia originating from the leakage, leads to a more profound sepsis. Another explanation might be that early leaks are not contained to the pelvis, leading to a more profound sepsis requiring early reoperations. Leakage with or without defunctioning stoma resulted in a different type of reinterventions and time-interval between surgery and reoperation.

Keywords: rectal cancer surgery, defunctioning stoma, anastomotic leakage, time-interval to reoperation

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10 Evaluation of a Personalized Online Decision Aid for Colorectal Cancer Screening: A Randomized Controlled Trial

Authors: Linda P. M. Pluymen, Mariska M. G. Leeflang, I. Stegeman, Henock G. Yebyo, Anne E. M. Brabers, Patrick M. Bossuyt, E. Dekker, Anke J. Woudstra, Mirjam P. Fransen

Abstract:

Weighing the benefits and harms of colorectal cancer screening can be difficult for individuals. An existing online decision aid was expanded with a benefit-harm analysis to help people make an informed decision about participating in colorectal cancer screening. In a randomized controlled trial, we investigated whether those in the intervention group who used the decision aid with benefit-harm analysis were more certain about their decision than those in the control group who used the decision aid without benefit-harm analysis. Participants were 623 (39% of those invited) men and women aged 45 until 75 years old. Analyses were performed in those 386 participants (62%) who reported to have completed the entire decision aid. No statistically significant differences were observed between intervention and control group in decisional conflict score (mean difference 2.4, 95% CI -0.9, 5.6), clarity of values (mean difference 1.0, 95% CI -4.4, 6.6), deliberation score (mean difference 0.5, 95% CI -0.6, 1.7), anxiety score (mean difference 0.0, 95% CI -0.3, 0.3) and risk perception score (mean difference 0.1, -0.1, 0.3). Adding a benefit-harm analysis to an online decision aid did not improve informed decision making about participating in colorectal cancer screening.

Keywords: benefit-harm analysis, decision aid, informed decision making, personalized decision making

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9 Kinetics of Phytochemicals and Antioxidant Activity during Thermal Treatment of Cape Gooseberry (Physalis peruviana L)

Authors: Mary-Luz Olivares-Tenorio, Ruud Verkerk, Matthijs Dekker, Martinus A. J. S. van Boekel

Abstract:

Cape gooseberry, the fruit of the plant Physalis peruviana L. has gained interest in research given its contents of promising health-promoting compounds like contents. The presence of carotenoids, ascorbic acid, minerals, polyphenols, vitamins and antioxidants. This project aims to study thermal stability of β-carotene, ascorbic acid, catechin and epicatechin and antioxidant activity in the matrix of the Cape Gooseberry. Fruits were obtained from a Colombian field in Cundinamarca. Ripeness stage was 4 (According to NTC 4580, corresponding to mature stage) at the moment of the experiment. The fruits have been subjected to temperatures of 40, 60, 80, 100 and 120°C for several times. β-Carotene, ascorbic acid, catechin and epicatechin content were assessed with HPLC and antioxidant activity with the DPPH method. β-Carotene was stable upon 100°C, and showed some degradation at 120°C. The same behavior was observed for epicatechin. Catechin increased during treatment at 40°C, at 60°C it remained stable and it showed degradation at 80°C, 100°C and 120°C that could be described by a second order kinetic model. Ascorbic acid was the most heat-sensitive of the analyzed compounds. It showed degradation at all studied temperatures, and could be described by a first order model. The activation energy for ascorbic acid degradation in cape gooseberry was 46.0 kJ/mol and its degradation rate coefficient at 100 °C was 6.53 x 10-3 s-1. The antioxidant activity declined for all studied temperatures. Results from this study showed that cape gooseberry is an important source of different health-promoting compounds and some of them are stable to heat. That makes this fruit a suitable raw material for processed products such as jam, juices and dehydrated fruit, giving the consumer a good intake of these compounds.

Keywords: goldenberry, health-promoting compounds, phytochemical, processing, heat treatment

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8 Biodiversity Affects Bovine Tuberculosis (bTB) Risk in Ethiopian Cattle: Prospects for Infectious Disease Control

Authors: Sintayehu W. Dejene, Ignas M. A. Heitkönig, Herbert H. T. Prins, Zewdu K. Tessema, Willem F. de Boer

Abstract:

Current theories on diversity-disease relationships describe host species diversity and species identity as important factors influencing disease risk, either diluting or amplifying disease prevalence in a community. Whereas the simple term ‘diversity’ embodies a set of animal community characteristics, it is not clear how different measures of species diversity are correlated with disease risk. We, therefore, tested the effects of species richness, Pielou’s evenness and Shannon’s diversity on bTB risk in cattle in the Afar Region and Awash National Park between November 2013 and April 2015. We also analysed the identity effect of a particular species and the effect of host habitat use overlap on bTB risk. We used the comparative intradermal tuberculin test to assess the number of bTB infected cattle. Our results suggested a dilution effect through species evenness. We found that the identity effect of greater kudu - a maintenance host – confounded the dilution effect of species diversity on bTB risk. bTB infection was positively correlated with habitat use overlap between greater kudu and cattle. Different diversity indices have to be considered together for assessing diversity-disease relationships, for understanding the underlying causal mechanisms. We posit that unpacking diversity metrics is also relevant for formulating control strategies to manage cattle in ecosystems characterized by seasonally limited resources and intense wildlife-livestock interactions.

Keywords: evenness, diversity, greater kudu, identity effect, maintenance hosts, multi-host disease ecology, habitat use overlap

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7 Mechanisms of Action in Mindfulness-Based Cognitive Therapy (MBCT) and Mindfulness-Based Stress Reduction (MBSR) in People with Physical and/or Psychological Conditions: A Systematic Review

Authors: Modi Alsubaie, Willem Kuyken, Rebecca Abbott, Barnaby Dunn, Chris Dickens, Tina Keil, William Henley

Abstract:

Background: Recently, there has been an increased interest in studying the effects of mindfulness-based interventions for people with psychological and physical problems. However, the mechanisms of action in these interventions that lead to beneficial physical and psychological outcomes have yet to be clearly identified. Purpose: The aim of this paper is to review, systematically, the evidence to date on the mechanisms of action in mindfulness interventions in populations with physical and/or psychological conditions. Method: Searches of seven databases (PsycINFO, Medline (Ovid), Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, AMED, ClinicalTrials.gov) were undertaken in June 2014 and July 2015. We evaluated to what extent the studies we identified met the criteria suggested by Kazdin for establishing mechanisms of action within a psychological treatment (2007, 2009). Results: We identified four trials examining mechanisms of mindfulness interventions in those with comorbid psychological and physical health problems and 14 in those with psychological conditions. These studies examined a diverse range of potential mechanisms, including mindfulness and rumination. Of these candidate mechanisms, the most consistent finding was that greater self-reported change in mindfulness mediated superior clinical outcomes. However, very few studies fully met the Kazdin criteria for examining treatment mechanisms. Conclusion: There was evidence that global changes in mindfulness are linked to better outcomes. This evidence pertained more to interventions targeting psychological rather than physical health conditions. While there is promising evidence that MBCT/MBSR intervention effects are mediated by hypothesised mechanisms, there is a lack of methodological rigour in the field of testing mechanisms of action for both MBCT and MBSR, which precludes definitive conclusions.

Keywords: MBCT, MBSR, mechanisms, physical conditions, psychological conditions, systematic review

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6 Surprise Fraudsters Before They Surprise You: A South African Telecommunications Case Study

Authors: Ansoné Human, Nantes Kirsten, Tanja Verster, Willem D. Schutte

Abstract:

Every year the telecommunications industry suffers huge losses due to fraud. Mobile fraud, or generally, telecommunications fraud is the utilisation of telecommunication products or services to acquire money illegally from or failing to pay a telecommunication company. A South African telecommunication operator developed two internal fraud scorecards to mitigate future risks of application fraud events. The scorecards aim to predict the likelihood of an application being fraudulent and surprise fraudsters before they surprise the telecommunication operator by identifying fraud at the time of application. The scorecards are utilised in the vetting process to evaluate the applicant in terms of the fraud risk the applicant would present to the telecommunication operator. Telecommunication providers can utilise these scorecards to profile customers, as well as isolate fraudulent and/or high-risk applicants. We provide the complete methodology utilised in the development of the scorecards. Furthermore, a Determination and Discrimination (DD) ratio is provided in the methodology to select the most influential variables from a group of related variables. Throughout the development of these scorecards, the following was revealed regarding fraudulent cases and fraudster behaviour within the telecommunications industry: Fraudsters typically target high-value handsets. Furthermore, debit order dates scheduled for the end of the month have the highest fraud probability. The fraudsters target specific stores. Applicants who acquire an expensive package and receive a medium-income, as well as applicants who obtain an expensive package and receive a high income, have higher fraud percentages. If one month prior to application, the status of an account is already in arrears (two months or more), the applicant has a high probability of fraud. The applicants with the highest average spend on calls have a higher probability of fraud. If the amount collected changes from month to month, the likelihood of fraud is higher. Lastly, young and middle-aged applicants have an increased probability of being targeted by fraudsters than other ages.

Keywords: application fraud scorecard, predictive modeling, regression, telecommunications

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5 Multiscale Modeling of Damage in Textile Composites

Authors: Jaan-Willem Simon, Bertram Stier, Brett Bednarcyk, Evan Pineda, Stefanie Reese

Abstract:

Textile composites, in which the reinforcing fibers are woven or braided, have become very popular in numerous applications in aerospace, automotive, and maritime industry. These textile composites are advantageous due to their ease of manufacture, damage tolerance, and relatively low cost. However, physics-based modeling of the mechanical behavior of textile composites is challenging. Compared to their unidirectional counterparts, textile composites introduce additional geometric complexities, which cause significant local stress and strain concentrations. Since these internal concentrations are primary drivers of nonlinearity, damage, and failure within textile composites, they must be taken into account in order for the models to be predictive. The macro-scale approach to modeling textile-reinforced composites treats the whole composite as an effective, homogenized material. This approach is very computationally efficient, but it cannot be considered predictive beyond the elastic regime because the complex microstructural geometry is not considered. Further, this approach can, at best, offer a phenomenological treatment of nonlinear deformation and failure. In contrast, the mesoscale approach to modeling textile composites explicitly considers the internal geometry of the reinforcing tows, and thus, their interaction, and the effects of their curved paths can be modeled. The tows are treated as effective (homogenized) materials, requiring the use of anisotropic material models to capture their behavior. Finally, the micro-scale approach goes one level lower, modeling the individual filaments that constitute the tows. This paper will compare meso- and micro-scale approaches to modeling the deformation, damage, and failure of textile-reinforced polymer matrix composites. For the mesoscale approach, the woven composite architecture will be modeled using the finite element method, and an anisotropic damage model for the tows will be employed to capture the local nonlinear behavior. For the micro-scale, two different models will be used, the one being based on the finite element method, whereas the other one makes use of an embedded semi-analytical approach. The goal will be the comparison and evaluation of these approaches to modeling textile-reinforced composites in terms of accuracy, efficiency, and utility.

Keywords: multiscale modeling, continuum damage model, damage interaction, textile composites

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4 Effective Affordable Housing Finance in Developing Economies: An Integration of Demand and Supply Solutions

Authors: Timothy Akinwande, Eddie Hui, Karien Dekker

Abstract:

Housing the urban poor remains a persistent challenge, despite evident research attention over many years. It is, therefore, pertinent to investigate affordable housing provision challenges with novel approaches. For innovative solutions to affordable housing constraints, it is apposite to thoroughly examine housing solutions vis a vis the key elements of the housing supply value chain (HSVC), which are housing finance, housing construction and land acquisition. A pragmatic analysis will examine affordable housing solutions from demand and supply perspectives to arrive at consolidated solutions from bilateral viewpoints. This study thoroughly examined informal housing finance strategies of the urban poor and diligently investigated expert opinion on affordable housing finance solutions. The research questions were: (1) What mutual grounds exist between informal housing finance solutions of the urban poor and housing expert solutions to affordable housing finance constraints in developing economies? (2) What are effective approaches to affordable housing finance in developing economies from an integrated demand - supply perspective? Semi-structured interviews were conducted in the 5 largest slums of Lagos, Nigeria, with 40 informal settlers for demand-oriented solutions, while focus group discussion and in-depth interviews were conducted with 12 housing experts in Nigeria for supply-oriented solutions. Following a rigorous thematic, content and descriptive analyses of data using NVivo and Excel, findings ascertained mutual solutions from both demand and supply standpoints that can be consolidated into more effective affordable housing finance solutions in Nigeria. Deliberate finance models that recognise and include the finance realities of the urban poor was found to be the most significant supply-side housing finance solution, representing 25.4% of total expert responses. Findings also show that 100% of sampled urban poor engage in vocations where they earn little irregular income or zero income, limiting their housing finance capacities and creditworthiness. Survey revealed that the urban poor are involved in community savings and employ microfinance institutions within the informal settlements to tackle their housing finance predicaments. These are informal finance models of the urban poor, revealing common grounds between demand and supply solutions for affordable housing financing. Effective, affordable housing approach will be to modify, institutionalise and incorporate the informal finance strategies of the urban poor into deliberate government policies. This consolidation of solutions from demand and supply perspectives can eliminate the persistent misalliance between affordable housing demand and affordable housing supply. This study provides insights into mutual housing solutions from demand and supply perspectives, and findings are informative for effective, affordable housing provision approaches in developing countries. This study is novel in consolidating affordable housing solutions from demand and supply viewpoints, especially in relation to housing finance as a key component of HSVC. The framework for effective, affordable housing finance in developing economies from a consolidated viewpoint generated in this study is significant for the achievement of sustainable development goals, especially goal 11 for sustainable, resilient and inclusive cities. Findings are vital for future housing studies.

Keywords: affordable housing, affordable housing finance, developing economies, effective affordable housing, housing policy, urban poor, sustainable development goal, sustainable affordable housing

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3 Evaluating the Teaching and Learning Value of Tablets

Authors: Willem J. A. Louw

Abstract:

The wave of new advanced computing technology that has been developed during the recent past has significantly changed the way we communicate, collaborate and collect information. It has created a new technology environment and paradigm in which our children and students grow-up and this impacts on their learning. Research confirmed that Generation Y students have a preference for learning in the new technology environment. The challenge or question is: How do we adjust our teaching and learning to make the most of these changes. The complexity of effective and efficient teaching and learning must not be underestimated and changes must be preceded by proper objective research to prevent any haphazard developments that could do more harm than benefit. A blended learning approach has been used in the Forestry department for a few numbers of years including the use of electronic-peer assisted learning (e-pal) in a fixed-computer set-up within a learning management system environment. It was decided to extend the investigation and do some exploratory research by using a range of different Tablet devices. For this purpose, learning activities or assignments were designed to cover aspects of communication, collaboration and collection of information. The Moodle learning management system was used to present normal module information, to communicate with students and for feedback and data collection. Student feedback was collected by using an online questionnaire and informal discussions. The research project was implemented in 2013, 2014 and 2015 amongst first and third-year students doing a forestry three-year technical tertiary qualification in commercial plantation management. In general, more than 80% of the students alluded to that the device was very useful in their learning environment while the rest indicated that the devices were not very useful. More than ninety percent of the students acknowledged that they would like to continue using the devices for all of their modules whilst the rest alluded to functioning efficiently without the devices. Results indicated that information collection (access to resources) was rated the highest advantageous factor followed by communication and collaboration. The main general advantages of using Tablets were listed by the students as being mobility (portability), 24/7 access to learning material and information of any kind on a user friendly device in a Wi-Fi environment, fast computing process speeds, saving time, effort and airtime through skyping and e-mail, and use of various applications. Ownership of the device is a critical factor while the risk was identified as a major potential constraint. Significant differences were reported between the different types and quality of Tablets. The preferred types are those with a bigger screen and the ones with overall better functionality and quality features. Tablets significantly increase the collaboration, communication and information collection needs of the students. It does, however, not replace the need of a computer/laptop because of limited storage and computation capacity, small screen size and inefficient typing.

Keywords: tablets, teaching, blended learning, tablet quality

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2 Feasibility and Acceptability of Mindfulness-Based Cognitive Therapy in People with Depression and Cardiovascular Disorders: A Feasibility Randomised Controlled Trial

Authors: Modi Alsubaie, Chris Dickens, Barnaby Dunn, Andy Gibson, Obioha Ukoumunned, Alison Evans, Rachael Vicary, Manish Gandhi, Willem Kuyken

Abstract:

Background: Depression co-occurs in 20% of people with cardiovascular disorders, can persist for years and predicts worse physical health outcomes. While psychosocial treatments have been shown to effectively treat acute depression in those with comorbid cardiovascular disorders, to date there has been no evaluation of approaches aiming to prevent relapse and treat residual depression symptoms in this group. Therefore, the current study aimed to examine the feasibility and acceptability of a randomised controlled trial design evaluating an adapted version of mindfulness-based cognitive therapy (MBCT) designed specifically for people with co-morbid depression and cardiovascular disorders. Methods: A 3-arm feasibility randomised controlled trial was conducted, comparing MBCT adapted for people with cardiovascular disorders plus treatment as usual (TAU), mindfulness-based stress reduction (MBSR) plus TAU, and TAU alone. Participants completed a set of self-report measures of depression severity, anxiety, quality of life, illness perceptions, mindfulness, self-compassion and affect and had their blood pressure taken immediately before, immediately after, and three months following the intervention. Those in the adapted-MBCT arm additionally underwent a qualitative interview to gather their views about the adapted intervention. Results: 3400 potentially eligible participants were approached when attending an outpatient appointment at a cardiology clinic or via a GP letter following a case note search. 242 (7.1%) were interested in taking part, 59 (1.7%) were screened as being suitable, and 33 (<1%) were eventually randomised to the three groups. The sample was heterogeneous in terms of whether they reported current depression or had a history of depression and the time since the onset of cardiovascular disease (one to 25 years). Of 11 participants randomised to adapted MBCT seven completed the full course, levels of home mindfulness practice were high, and positive qualitative feedback about the intervention was given. Twenty-nine out of 33 participants randomised completed all the assessment measures at all three-time points. With regards to the primary outcome (depression), five out of the seven people who completed the adapted MBCT and three out of five under MBSR showed significant clinical change, while in TAU no one showed any clinical change at the three-month follow-up. Conclusions: The adapted MBCT intervention was feasible and acceptable to participants. However, aspects of the trial design were not feasible. In particular, low recruitment rates were achieved, and there was a high withdrawal rate between screening and randomisation. Moreover, the heterogeneity in the sample was high meaning the adapted intervention was unlikely to be well tailored to all participants needs. This suggests that if the decision is made to move to a definitive trial, study recruitment procedures will need to be revised to more successfully recruit a target sample that optimally matches the adapted intervention.

Keywords: mindfulness-based cognitive therapy (MBCT), depression, cardiovascular disorders, feasibility, acceptability

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1 Plasma Levels of Collagen Triple Helix Repeat Containing 1 (CTHRC1) as a Potential Biomarker in Interstitial Lung Disease

Authors: Rijnbout-St.James Willem, Lindner Volkhard, Scholand Mary Beth, Ashton M. Tillett, Di Gennaro Michael Jude, Smith Silvia Enrica

Abstract:

Introduction: Fibrosing lung diseases are characterized by changes in the lung interstitium and are classified based on etiology: 1) environmental/exposure-related, 2) autoimmune-related, 3) sarcoidosis, 4) interstitial pneumonia, and 4) idiopathic. Among interstitial lung diseases (ILD) idiopathic forms, idiopathic pulmonary fibrosis (IPF) is the most severe. Pathogenesis of IPF is characterized by an increased presence of proinflammatory mediators, resulting in alveolar injury, where injury to alveolar epithelium precipitates an increase in collagen deposition, subsequently thickening the alveolar septum and decreasing gas exchange. Identifying biomarkers implicated in the pathogenesis of lung fibrosis is key to developing new therapies and improving the efficacy of existing therapies. The transforming growth factor-beta (TGF-B1), a mediator of tissue repair associated with WNT5A signaling, is partially responsible for fibroblast proliferation in ILD and is the target of Pirfenidone, one of the antifibrotic therapies used for patients with IPF. Canonical TGF-B signaling is mediated by the proteins SMAD 2/3, which are, in turn, indirectly regulated by Collagen Triple Helix Repeat Containing 1 (CTHRC1). In this study, we tested the following hypotheses: 1) CTHRC1 is more elevated in the ILD cohort compared to unaffected controls, and 2) CTHRC1 is differently expressed among ILD types. Material and Methods: CTHRC1 levels were measured by ELISA in 171 plasma samples from the deidentified University of Utah ILD cohort. Data represent a cohort of 131 ILD-affected participants and 40 unaffected controls. CTHRC1 samples were categorized by a pulmonologist based on affectation status and disease subtypes: IPF (n = 45), sarcoidosis (4), nonspecific interstitial pneumonia (16), hypersensitivity pneumonitis (n = 7), interstitial pneumonia (n=13), autoimmune (n = 15), other ILD - a category that includes undifferentiated ILD diagnoses (n = 31), and unaffected controls (n = 40). We conducted a single-factor ANOVA of plasma CTHRC1 levels to test whether CTHRC1 variance among affected and non-affected participants is statistically significantly different. In-silico analysis was performed with Ingenuity Pathway Analysis® to characterize the role of CTHRC1 in the pathway of lung fibrosis. Results: Statistical analyses of CTHRC1 in plasma samples indicate that the average CTHRC1 level is significantly higher in ILD-affected participants than controls, with the autoimmune ILD being higher than other ILD types, thus supporting our hypotheses. In-silico analyses show that CTHRC1 indirectly activates and phosphorylates SMAD3, which in turn cross-regulates TGF-B1. CTHRC1 also may regulate the expression and transcription of TGFB-1 via WNT5A and its regulatory relationship with CTNNB1. Conclusion: In-silico pathway analyses demonstrate that CTHRC1 may be an important biomarker in ILD. Analysis of plasma samples indicates that CTHRC1 expression is positively associated with ILD affectation, with autoimmune ILD having the highest average CTHRC1 values. While characterizing CTHRC1 levels in plasma can help to differentiate among ILD types and predict response to Pirfenidone, the extent to which plasma CTHRC1 level is a function of ILD severity or chronicity is unknown.

Keywords: interstitial lung disease, CTHRC1, idiopathic pulmonary fibrosis, pathway analyses

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