Publications by authors named "Carolin Schneider"
Proton pump inhibitors and all-cause mortality risk among cancer patients.
World J Clin Oncol
January 2025
Background: Proton pump inhibitors (PPIs) are widely used, including among cancer patients, to manage gastroesophageal reflux and other gastric acid-related disorders. Recent evidence suggests associations between long-term PPI use and higher risks for various adverse health outcomes, including greater mortality.
Aim: To investigate the association between PPI use and all-cause mortality among cancer patients by a comprehensive analysis after adjustment for various confounders and a robust methodological approach to minimize bias.
Hepatocellular cancer (HCC) therapy is in need for an ideal companion diagnostic. Preclinical experimental studies have identified the insulin receptor (IR) and its synergistic counterpart, the IGF1 receptor (IGF1R), as relevant in HCC development, and the ligands IGF1 and IGF2 have been found to be elevated in HCC. This study aimed to bridge the gap to the clinical setting and explore whether the IR or the IGF1R would be of prognostic significance and would be associated with clinicopathologic parameters in HCC patients.
View Article and Find Full Text PDFBackground & Aim: An unbiased genome-first approach can expand the molecular understanding of specific genes in disease-agnostic biobanks for deeper phenotyping. represents a good candidate for this approach due to its known association with steatotic liver disease (SLD).
Methods: We screened participants with whole-exome sequences in the Penn Medicine Biobank (PMBB, n >40,000) and the UK Biobank (UKB, n >200,000) for protein-altering variants in and evaluated their association with liver phenotypes and clinical outcomes.
Article Synopsis
- ACLF is a complex condition characterized by acute worsening of liver disease and organ failure, prompting this study to create a machine learning model to predict patient mortality in the ICU.
- The research analyzed data from 206 ICU patients at RWTH Aachen University Hospital and developed a predictive model using logistic regression, achieving an impressive accuracy with an AUROC of 0.96.
- The resulting Aachen ACLF ICU (ACICU) score outperforms existing mortality predictors and provides a user-friendly tool for assessing the likelihood of mortality in critically ill patients with ACLF.
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects up to 30% of Western populations. While obesity is a recognized risk factor, MASLD does not develop in all obese individuals, highlighting the need to understand genetic and environmental interactions. The PNPLA3 I148M variant has been identified as a key genetic risk factor, significantly increasing the likelihood of MASLD development and progression.
View Article and Find Full Text PDFBackground & Aims: Homozygous Pi∗Z mutation in alpha-1 antitrypsin (Pi∗ZZ genotype) predisposes to pulmonary loss-of-function and hepatic gain-of-function injury. To facilitate selection into clinical trials typically targeting only 1 organ, we systematically evaluated an international, multicenter, longitudinal, Pi∗ZZ cohort to uncover natural disease course and surrogates for future liver- and lung-related endpoints.
Methods: Cohort 1 recruited 737 Pi∗ZZ individuals from 25 different centers without known liver comorbidities who received a baseline clinical and laboratory assessment as well as liver stiffness measurement (LSM).
Article Synopsis
- This study investigates the link between incretin-based drugs (GLP-1RAs and DPP-4Is) and the risk of cholangiocarcinoma (CCA) in patients with type 2 diabetes in the U.S.
- It analyzed data from over 3.8 million patients and found that GLP-1RA users had a 51% reduced risk of developing CCA after one year, while DPP-4I users had a 23% reduction.
- The findings suggest that both drug classes are safe for T2DM patients, with GLP-1RAs potentially lowering the risk of CCA compared to other treatments.
Background: Arbuscular mycorrhizas (AM) are the most widespread terrestrial symbiosis and are both a key determinant of plant health and a major contributor to ecosystem processes through their role in biogeochemical cycling. Until recently, it was assumed that the fungi which form AM comprise the subphylum Glomeromycotina (G-AMF), and our understanding of the diversity and ecosystem roles of AM is based almost exclusively on this group. However recent evidence shows that fungi which form the distinctive 'fine root endophyte' (FRE) AM morphotype are members of the subphylum Mucoromycotina (M-AMF), so that AM symbioses are actually formed by two distinct groups of fungi.
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- * Direct KRAS inhibitors are showing promise in clinical trials, but resistance to treatment is a concern, prompting the search for combination therapies.
- * Unbiased drug screening identified effective combinations involving SOS1 inhibitors, PTPN11/SHP2 inhibitors, and multi-kinase inhibitors, validated using a unique KRAS-mutated patient-derived organoid model.
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects approximately 20%-30% of the general population and is linked to high-caloric western style diet. However, there are little data that specific nutrients might help to prevent steatosis.
Methods: We analysed the UK Biobank (ID 71300) 24 h-nutritional assessments and investigated the association between nutrient intake calculated from food questionnaires and hepatic steatosis indicated by imaging or ICD10-coding.
Background And Aims: Alpha-1 antitrypsin deficiency is an inherited disorder caused by alpha-1 antitrypsin (AAT) mutations. We analysed the association between alcohol intake and liver-related parameters in individuals with the heterozygous/homozygous Pi*Z AAT variant (Pi*MZ/Pi*ZZ genotype) found in the United Kingdom Biobank and the European Alpha1 liver consortium.
Methods: Reported alcohol consumption was evaluated in two cohorts: (i) the community-based United Kingdom Biobank (17 145 Pi*MZ, 141 Pi*ZZ subjects, and 425 002 non-carriers [Pi*MM]); and (ii) the European Alpha1 liver consortium (561 Pi*ZZ individuals).
Article Synopsis
- Cancer cells adapt to various stresses, including those from treatments, through metabolic adaptability, focusing on the energy sensor AMP-activated protein kinase (AMPK).
- In pancreatic ductal adenocarcinoma (PDAC), high levels of AMPK expression and activity were observed, leading to the identification of PF-3758309 as a potential AMPK inhibitor through drug repurposing.
- PF-3758309 not only demonstrates pre-clinical effectiveness in PDAC models but also helps sensitizes cancer cells to ferroptosis inducers, paving the way for AMPK-targeted therapies in combination treatments for this type of cancer.
Article Synopsis
- This analysis explores the optimal amount of cognitive behavioral therapy (CBT) needed to effectively treat major depressive disorder, focusing on the number of therapy sessions as the "dose."
- A systematic review of 72 studies with over 7,000 participants revealed that the most significant improvement in depression symptoms typically occurs within the first eight sessions of CBT, after which progress continues but at a slower rate.
- The findings suggest that shorter CBT interventions might be effective for symptom relief, but further research is needed to understand long-term effects and benefits beyond just symptom reduction.
Article Synopsis
- Dealing with different sequence formats and reference genomes is difficult in genetic research, leading to the need for tools that simplify this process.
- The Sequence Conversion and Analysis Toolbox (SeqCAT) has been created to help researchers standardize and convert gene variant coordinates efficiently through a user-friendly web interface and API for automation.
- With features like converting protein positions to DNA and checking gene fusions, SeqCAT offers 14 applications to cover a variety of genetic research needs and is accessible online.
Critical illness and sepsis may cause organ failure and are recognized as mortality drivers in hospitalized patients. Neuropilin-1 (NRP-1) is a multifaceted transmembrane protein involved in the primary immune response and is expressed in immune cells such as T and dendritic cells. The soluble form of NRP-1 (sNRP-1) acts as an antagonist to NRP-1 by scavenging its ligands.
View Article and Find Full Text PDFBackground: The ERLIN1 p.Ile291Val single-nucleotide polymorphism (rs2862954) is associated with protection from steatotic liver disease (SLD), but effects of this variant on metabolic phenotypes remain uncertain.
Methods: Metabolic phenotypes and outcomes associated with ERLIN1 p.
Arbuscular mycorrhizal fungi (AMF) play a crucial role in enhancing plant growth, but their use in agriculture is limited due to several constraints. Elevated soil phosphate levels resulting from fertilization practices strongly inhibit fungal development and reduce mycorrhizal growth response. Here, we investigated the possibility of adapting to high phosphate (Pi) levels to improve its tolerance.
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- The study investigates the association between a common variant of the MLXIPL gene, specifically Gln241His, and its impact on metabolic health, particularly regarding triglyceride levels and steatotic liver disease (SLD).
- Findings from two large biobanks indicate that individuals with this genetic variant often have lower triglyceride levels and certain liver enzymes but are at a higher risk for SLD, especially if they are female, obese, or carry another specific variant (PNPLA3 I148M).
- The results suggest that targeting the MLXIPL pathway could be a potential strategy for treating SLD and related conditions, but further research is required to understand the underlying mechanisms.
Article Synopsis
- Primary biliary cholangitis (PBC) is a chronic liver disease that can lead to serious complications like fibrosis and cirrhosis; this study examines its effects on health outcomes and metabolic changes in a UK population.
- The study involved 454 PBC patients and 908 matched controls, analyzing metabolic profiles and comorbidities, showing that PBC patients experienced higher rates of several diseases and almost triple the mortality rate compared to controls.
- Findings suggest early detection and treatment of PBC could improve patient outcomes, as morbidity in PBC isn't solely linked to liver disease severity, highlighting the complex health impacts of this condition.
Article Synopsis
- - Dirofilaria immitis is a parasitic worm that causes heartworm disease mainly in dogs, and there's rising concern about its resistance to standard preventative treatments known as macrocyclic lactones (MLs) in the USA.
- - Recent studies show that some D. immitis strains in the USA have distinct genetic traits that help identify their resistance to MLs, including specific genetic markers (SNPs) useful for tracking the spread of this resistance.
- - Research involving laboratory-maintained and European clinical samples indicates that while there is resistance in the USA, many genotypes in Europe still respond well to ML treatments, highlighting the need for effective monitoring and compliance with prevention strategies.
Article Synopsis
- A study assessed the prevalence of at-risk metabolic dysfunction-associated steatohepatitis (at-risk MASH) using liver MRI data from 40,189 UK Biobank participants.
- Among those, 27% showed signs of steatotic liver disease (SLD), with 89% classified as metabolic dysfunction-associated steatotic liver disease (MASLD) and only 2.2% identified as at-risk MASH, which is 0.6% of the general population.
- The at-risk MASH group had the highest liver fat and BMI, indicating severe metabolic and inflammatory issues, with notable differences in prevalence based on sex and BMI that highlight the need for targeted treatment strategies.
Article Synopsis
- * Research by Santofimia-Castano et al. highlights NUPR1, a protein that regulates KRAS-related stress granules, as a potential therapeutic target.
- * The small molecule inhibitor ZW-115 can block stress granule formation and induce cell death in KRAS-expressing PDAC cells, suggesting that targeting stress granules may be an effective approach for treating PDAC.