The high-resolution molecular portrait of coffee: A gateway to insights into its roasting chemistry and comprehensive authenticity profiles.

The direct-infusion of 130 coffee samples into a Fourier-transform ion cyclotron mass spectrometer (FT-ICR-MS) provided an ultra-high resolution perspective on the molecular complexity of coffee: The exceptional resolving power and mass accuracy (± 0.2 ppm) facilitated the annotation of unambiguous molecular formulas to 11,500 mass signals. Utilizing this molecular diversity, we extracted hundreds of compound signals linked to the roasting process through guided Orthogonal Partial Least Squares (OPLS) analysis.

Evolution of in a mouse model of inflammatory bowel disease leads to a disease-specific bacterial genotype and trade-offs with clinical relevance.

Inflammatory bowel disease (IBD) is a persistent inflammatory condition that affects the gastrointestinal tract and presents significant challenges in its management and treatment. Despite the knowledge that within-host bacterial evolution occurs in the intestine, the disease has rarely been studied from an evolutionary perspective. In this study, we aimed to investigate the evolution of resident bacteria during intestinal inflammation and whether- and how disease-related bacterial genetic changes may present trade-offs with potential therapeutic importance.

Pralsetinib in Patients with Advanced/Metastatic Rearranged During Transfection (RET)-Altered Thyroid Cancer: Updated Efficacy and Safety Data from the ARROW Study.

Rearranged during transfection () alterations are targetable oncogenic drivers in thyroid cancer. Primary data from the open-label, phase 1/2 ARROW study demonstrated clinical activity and manageable safety with pralsetinib, a selective RET inhibitor, in patients with advanced/metastatic -altered thyroid cancer. We present an updated analysis with more patients and longer follow-up.

Cluster Analysis Statistical Spectroscopy for the Identification of Metabolites in H NMR Metabolomics.

Metabolite identification in non-targeted NMR-based metabolomics remains a challenge. While many peaks of frequently occurring metabolites are assigned, there is a high number of unknowns in high-resolution NMR spectra, hampering biological conclusions for biomarker analysis. Here, we use a cluster analysis approach to guide peak assignment via statistical correlations, which gives important information on possible structural and/or biological correlations from the NMR spectrum.

Long-Term Efficacy and Safety of Entrectinib in Fusion-Positive NSCLC.

Introduction: Entrectinib is an approved tyrosine kinase inhibitor (TKI) for fusion-positive NSCLC. An updated integrated analysis of entrectinib from the ALKA-372-001, STARTRK-1, and STARTRK-2 trials is presented, with substantially longer follow-up, more patients, and the first description of the median overall survival (OS). An exploratory analysis of entrectinib in fusion-positive NSCLC with the central nervous system (CNS)-only progression post-crizotinib is reported.

Bezafibrate Reduces Elevated Hepatic Fumarate in Insulin-Deficient Mice.

Glucotoxic metabolites and pathways play a crucial role in diabetic complications, and new treatment options which improve glucotoxicity are highly warranted. In this study, we analyzed bezafibrate (BEZ) treated, streptozotocin (STZ) injected mice, which showed an improved glucose metabolism compared to untreated STZ animals. In order to identify key molecules and pathways which participate in the beneficial effects of BEZ, we studied plasma, skeletal muscle, white adipose tissue (WAT) and liver samples using non-targeted metabolomics (NMR spectroscopy), targeted metabolomics (mass spectrometry), microarrays and mitochondrial enzyme activity measurements, with a particular focus on the liver.

Updated Integrated Analysis of the Efficacy and Safety of Entrectinib in Patients With NTRK Fusion-Positive Solid Tumors.

Purpose: Entrectinib potently inhibits tropomyosin receptor kinases (TRKAs)/B/C and ROS1, and previously induced deep [objective response rate (ORR) 57.4%] and durable [median duration of response (DoR) 10.4 months] responses in adults with NTRK fusion-positive solid tumors from three phase I/II trials.

Data Processing Optimization in Untargeted Metabolomics of Urine Using Voigt Lineshape Model Non-Linear Regression Analysis.

Nuclear magnetic resonance (NMR) spectroscopy is well-established to address questions in large-scale untargeted metabolomics. Although several approaches in data processing and analysis are available, significant issues remain. NMR spectroscopy of urine generates information-rich but complex spectra in which signals often overlap.

Asc-1 regulates white versus beige adipocyte fate in a subcutaneous stromal cell population.

Adipose tissue expansion, as seen in obesity, is often metabolically detrimental causing insulin resistance and the metabolic syndrome. However, white adipose tissue expansion at early ages is essential to establish a functional metabolism. To understand the differences between adolescent and adult adipose tissue expansion, we studied the cellular composition of the stromal vascular fraction of subcutaneous adipose tissue of two and eight weeks old mice using single cell RNA sequencing.

Impact of β-glycerophosphate on the bioenergetic profile of vascular smooth muscle cells.

In chronic kidney disease, hyperphosphatemia is a key pathological factor promoting medial vascular calcification, a common complication associated with cardiovascular events and mortality. This active pathophysiological process involves osteo-/chondrogenic transdifferentiation of vascular smooth muscle cells (VSMCs) via complex intracellular mechanisms that are still incompletely understood. Little is known about the effects of phosphate on the bioenergetic profile of VSMCs during the onset of this process.

Guidelines for the Use of Deuterium Oxide (DO) in H NMR Metabolomics.

In metabolomics, nuclear magnetic resonance (NMR) spectroscopy allows to identify and quantify compounds in biological samples. The sample preparation generally requires only few steps; however, an indispensable factor is the addition of a locking substance into the biofluid sample, such as deuterium oxide (DO). While creatinine loss in pure DO is well-described, the effects of different DO concentrations on the signal profile of biological samples are unknown.

Milk-Derived Amadori Products in Feces of Formula-Fed Infants.

Food processing of infant formula alters chemical structures, including the formation of Maillard reaction products between proteins and sugars. We detected early Maillard reaction products, so-called Amadori products, in stool samples of formula-fed infants. In total, four Amadori products (-deoxylactulosyllysine, -deoxyfructosyllysine, -deoxylactulosylleucylisoleucine, -deoxyfructosylleucylisoleucine) were identified by a combination of complementary nontargeted and targeted metabolomics approaches.

Chronic d-serine supplementation impairs insulin secretion.

Objective: The metabolic role of d-serine, a non-proteinogenic NMDA receptor co-agonist, is poorly understood. Conversely, inhibition of pancreatic NMDA receptors as well as loss of the d-serine producing enzyme serine racemase have been shown to modulate insulin secretion. Thus, we aim to study the impact of chronic and acute d-serine supplementation on insulin secretion and other parameters of glucose homeostasis.

Tandem HILIC-RP liquid chromatography for increased polarity coverage in food analysis.

Comprehensive non-targeted analysis of food products normally requires two complementary chromatographic runs to achieve maximum compound coverage. In this study, we present a sensitive tandem-LC method, which combines RP and HILIC separation in a single run. The setup consists of a C18 trap column and two subsequently coupled analytical columns (HILIC and C18) which are operated in parallel.

Increased urinary osmolyte excretion indicates chronic kidney disease severity and progression rate.

Background: Chronic kidney disease (CKD) is a recognized global health problem. While some CKD patients remain stable after initial diagnosis, others can rapidly progress towards end-stage renal disease (ESRD). This makes biomarkers capable of detecting progressive forms of CKD extremely valuable, especially in non-invasive biofluids such as urine.

Proteomics and Metabolomics for AKI Diagnosis.

Acute kidney injury (AKI) is a severe and frequent condition in hospitalized patients. Currently, no efficient therapy of AKI is available. Therefore, efforts focus on early prevention and potentially early initiation of renal replacement therapy to improve the outcome in AKI.

Chemical messages from an ancient buried bottle: metabolomics for wine archeochemistry.

Restoration works in the old Clunisian Saint-Vivant monastery in Burgundy revealed an unidentified wine bottle (SV1) dating between 1772 and 1860. Chemical evidence for SV1 origin and nature are presented here using non-targeted Fourier Transform Ion Cyclotron Resonance Mass Spectrometry and Nuclear Magnetic Resonance analyses. The SV1 chemical diversity was compared to red wines (Pinot Noir) from the Romanée Saint Vivant appellation and from six different vintages spanning from 1915 to 2009.

Impact of Dietary Resistant Starch on the Human Gut Microbiome, Metaproteome, and Metabolome.

Diet can influence the composition of the human microbiome, and yet relatively few dietary ingredients have been systematically investigated with respect to their impact on the functional potential of the microbiome. Dietary resistant starch (RS) has been shown to have health benefits, but we lack a mechanistic understanding of the metabolic processes that occur in the gut during digestion of RS. Here, we collected samples during a dietary crossover study with diets containing large or small amounts of RS.

Sulfonolipids as novel metabolite markers of Alistipes and Odoribacter affected by high-fat diets.

The gut microbiota generates a huge pool of unknown metabolites, and their identification and characterization is a key challenge in metabolomics. However, there are still gaps on the studies of gut microbiota and their chemical structures. In this investigation, an unusual class of bacterial sulfonolipids (SLs) is detected in mouse cecum, which was originally found in environmental microbes.

Single-Center Study Investigating Foreign Language Acquisition at School in Children, Adolescents, and Young Adults With Uni- or Bilateral Cochlear Implants in the Swiss German Population.

Objective: To evaluate foreign language acquisition at school in cochlear implant patients.

Study Design: Cohort study.

Setting: CI center.

Relationship of Serum Trimethylamine N-Oxide (TMAO) Levels with early Atherosclerosis in Humans.

Circulating trimethylamine N-Oxide (TMAO) levels predict cardiovascular disease (CVD), possibly by impacting on cholesterol metabolism and oxidative stress. Because hepatic TMAO production is regulated by insulin signalling and it is unclear whether and to what extent circulating TMAO levels associate with CVD risk, independently of insulin resistance and its important determinants fatty liver and visceral obesity, we have now addressed this question in 220 subjects who participated in the Tübingen Lifestyle Intervention Program. Visceral fat mass (r = 0.