Real-World Effectiveness and Safety of Selective JAK Inhibitors in Ulcerative Colitis and Crohn's Disease: A Retrospective, Multicentre Study.

: Data on the real-world effectiveness and safety of selective JAK inhibitors (JAKis) in ulcerative colitis (UC) and Crohn's disease (CD) are limited. : We conducted a multicentre, retrospective study to assess clinical, biochemical, and endoscopic outcomes of selective JAKis in bio-experienced UC and CD. : A total of 246 patients (mean age: 40.

Fragment-to-Lead Medicinal Chemistry Publications in 2023.

This Perspective summarizes successful fragment-to-lead (F2L) studies that were published in 2023 and is the ninth installment in an annual series. A tabulated summary of the relevant articles published in 2023 is provided (17 entries from 16 articles), and a comparison of the target classes, screening methods, and overall fragment or lead property trends for 2023 examples and for the combined entries over the years 2015-2023 is discussed. In addition, we identify several trends and innovations in the 2023 literature that promise to further increase the success of fragment-based drug discovery (FBDD), particularly in the areas of NMR and virtual screening, fragment library design, and fragment linking.

Evaluation of the Effectiveness and Safety of Mesenchymal Stem Cell Treatment in Fistulising Crohn's Disease: An International Real-Life Retrospective Multicentre Cohort Study.

Background: Perianal fistulas of Crohn's disease (CD) create a significant burden on patients' lives. However, the efficacy and safety of adipose-derived mesenchymal stem cell treatment are contradicting, and real-world evidence is lacking.

Aims: To examine the usability of darvadstrocel therapy in managing perianal CD.

Characterizing the role of unpredictability within different dimensions of early life adversity.

Dimensional models of early life adversity highlight the distinct roles of deprivation and threat in shaping neurocognitive development and mental health. However, relatively little is known about the role of unpredictability within each dimension. We estimated both the average levels of, and the temporal unpredictability of deprivation and threat exposure during adolescence in a high-risk, longitudinal sample of 1354 youth (Pathways to Desistance study).

Shotgun Analysis of Gut Microbiota with Body Composition and Lipid Characteristics in Crohn's Disease.

Alterations to intestinal microbiota are assumed to occur in the pathogenesis of inflammatory bowel disease (IBD). This study aims to analyze the association of fecal microbiota composition, body composition, and lipid characteristics in patients with Crohn's disease (CD). In our cross-sectional study, patients with CD were enrolled and blood and fecal samples were collected.

Long-Term Self-Management of Vaginal Cube Pessaries Can Improve Sexual Life in Patients with Pelvic Organ Prolapse, Results from a Secondary Analysis.

Introduction And Hypothesis: Currently, little is known about how daily self-management of cube pessaries influences sexual function. We hypothesized that removing the cube pessary prior to sexual activity did not negatively influence the sexual function, and pessary self-care did not lead to a deterioration of sexual wellbeing.

Methods: We conducted a planned secondary analysis of a prospective cohort study in which 214 patients with symptomatic pelvic organ prolapse (stage 2+) were enrolled (2015).

Efficacy, drug sustainability, and safety of ustekinumab treatment in Crohn's disease patients over three years.

Long-term data on ustekinumab in real-life Crohn's disease patients are still missing, though randomized controlled trials demonstrated it as a favorable therapeutic option. We aimed to evaluate ustekinumab's clinical efficacy, drug sustainability, and safety in a prospective, nationwide, multicenter Crohn's disease patient cohort with a three-year follow-up. Crohn's disease patients on ustekinumab treatment were consecutively enrolled from 9 Hungarian Inflammatory Bowel Disease centers between January 2019 and May 2020.

Network-driven cancer cell avatars for combination discovery and biomarker identification for DNA damage response inhibitors.

Combination therapy is well established as a key intervention strategy for cancer treatment, with the potential to overcome monotherapy resistance and deliver a more durable efficacy. However, given the scale of unexplored potential target space and the resulting combinatorial explosion, identifying efficacious drug combinations is a critical unmet need that is still evolving. In this paper, we demonstrate a network biology-driven, simulation-based solution, the Simulated Cell™.

Optimization of ultra-precision CBN turning of AISI D2 using hybrid GA-RSM and Taguchi-GRA statistic tools.

Ultra-precision turning is a crucial process in the manufacturing industry as it helps to produce parts with high dimensional accuracy, surface finish, and tolerance. The process is similar to traditional turning but is carried out under special circumstances to achieve greater precision and surface finish. The process can be applied to conventional structural materials, but the demand for machining hardened steels is increasing.

Unveiling the Role of Exosomes in the Pathophysiology of Sepsis: Insights into Organ Dysfunction and Potential Biomarkers.

Extracellular vesicles (EVs) are tools for intercellular communication, mediating molecular transport processes. Emerging studies have revealed that EVs are significantly involved in immune processes, including sepsis. Sepsis, a dysregulated immune response to infection, triggers systemic inflammation and multi-organ dysfunction, posing a life-threatening condition.

Long-term outcomes after endoscopic removal of malignant colorectal polyps: Results from a 10-year cohort.

Background: Choosing an optimal post-polypectomy management strategy of malignant colorectal polyps is challenging, and evidence regarding a surveillance-only strategy is limited.

Aim: To evaluate long-term outcomes after endoscopic removal of malignant colorectal polyps.

Methods: A single-center retrospective cohort study was conducted to evaluate outcomes after endoscopic removal of malignant colorectal polyps between 2010 and 2020.

"We're sinking": a qualitative interview-based study on stakeholder perceptions of structural and process limitations to the Canadian healthcare system.

Background: Despite longstanding efforts and calls for reform, Canada's incremental approach to healthcare changes has left the country lagging behind other OECD nations. Reform to the Canadian healthcare system is essential to develop a higher performing system. This study sought to gain a deeper understanding of the views of Canadian stakeholders on structural and process deficiencies and strategies to improve the Canadian healthcare system substantially and meaningfully.

Evidence for a competitive relationship between executive functions and statistical learning.

The ability of the brain to extract patterns from the environment and predict future events, known as statistical learning, has been proposed to interact in a competitive manner with prefrontal lobe-related networks and their characteristic cognitive or executive functions. However, it remains unclear whether these cognitive functions also possess a competitive relationship with implicit statistical learning across individuals and at the level of latent executive function components. In order to address this currently unknown aspect, we investigated, in two independent experiments (N = 186, N = 157), the relationship between implicit statistical learning, measured by the Alternating Serial Reaction Time task, and executive functions, measured by multiple neuropsychological tests.

Accuracy of the Pancolonic Modified Mayo Score in predicting the long-term outcomes of ulcerative colitis: a promising scoring system.

Background: Different endoscopic scoring systems for assessing ulcerative colitis (UC) severity are available. However, most of them are not correlated with disease extent.

Objectives: Our study aimed to compare the predictive value of the PanMay score the endoscopic Mayo (MES), Ulcerative Colitis Endoscopic Index of Severity (UCEIS), and Dublin score in predicting long-term outcomes of UC.

Integrative Epigenetic and Molecular Analysis Reveals a Novel Promoter for a New Isoform of the Transcription Factor TEAD4.

TEAD4 is a transcription factor that plays a crucial role in the Hippo pathway by regulating the expression of genes related to proliferation and apoptosis. It is also involved in the maintenance and differentiation of the trophectoderm during pre- and post-implantation embryonic development. An alternative promoter for the TEAD4 gene was identified through epigenetic profile analysis, and a new transcript from the intronic region of TEAD4 was discovered using the 5'RACE method.

Specifying the timescale of early life unpredictability helps explain the development of internalising and externalising behaviours.

Early life unpredictability is associated with both physical and mental health outcomes throughout the life course. Here, we classified adverse experiences based on the timescale on which they are likely to introduce variability in children's environments: variations unfolding over short time scales (e.g.

The Lectin Pathway of the Complement System-Activation, Regulation, Disease Connections and Interplay with Other (Proteolytic) Systems.

The complement system is the other major proteolytic cascade in the blood of vertebrates besides the coagulation-fibrinolytic system. Among the three main activation routes of complement, the lectin pathway (LP) has been discovered the latest, and it is still the subject of intense research. Mannose-binding lectin (MBL), other collectins, and ficolins are collectively termed as the pattern recognition molecules (PRMs) of the LP, and they are responsible for targeting LP activation to molecular patterns, e.

The neuropsychological profile of work addiction.

The objective of this study was to examine, for the first time, the neuropsychological aspects of work addiction, with a specific emphasis on the cognitive factors identified by theoretical models. While previous research has highlighted self-reported obsessiveness and impulsiveness in work addiction, this study sought to go beyond self-report measures by employing also neuropsychological reaction time tasks to assess executive functions. A total of 101 participants were categorized into two groups based on their Work Addiction Risk Test scores: a high-risk group (HWA; n = 39) and a low-risk group (LWA; n = 62) for work addiction.