Nathan Lawler

We investigated metabolite responses to different swimming intensities in 16 highly trained swimmers (9 males, 7 females, aged 16–24 years). After determining critical swimming speed (CS) with a 12 × 25 m maximal effort test, participants completed three swimming trials at moderate (below CS), heavy (at CS), and severe (above CS) intensities on separate days. Capillary blood samples (1 mL) were collected before and after each trial for metabolite profiling via mass spectrometry. Orthogonal partial least squares analysis (OPLS-DA) revealed distinct metabolite changes between moderate and severe intensity trials [R2X (cum): 0.56; R2Y(cum): 0.95, pR2Y: 0.02, pQ2: 0.02]. Free fatty acids (FFAs) 18:0, 20:0, 20:4, and 22:4 showed higher log2 fold changes (log2FC) after moderate compared to heavy and severe trials (all p < 0.01). Plasma lactate, pyruvate, alanine, and HDL-4 cholesterol concentrations had greater log2FC after heavy and severe trials than moderate (all p < 0.01). Males tended to show lower log2FC in FFA than females in the severe trial, though this was not significant. These findings demonstrate that swimming intensity influences metabolite profiles, with reduced lipid metabolism and increased TCA cycle activity as intensity rises. A 1 mL capillary blood sample can effectively capture these metabolic shifts.

SARS-CoV-2 infections in children lead to symptoms from mild respiratory illness to severe postacute sequelae of COVID-19, including multisystem inflammatory syndrome in Children (MIS-C). We conducted a metabolic profiling of 147 children's serum samples, including acute COVID-19 patients, MIS-C patients, and healthy controls. Using nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry, we measured 1101 metabolites. The results revealed distinct metabolic profiles in acute COVID-19 and MIS-C patients, with significant alterations in lipid classes. Both conditions exhibited an elevated Apo-B100/Apo-A1 ratio and increased serum inflammatory markers. MIS-C patients showed unique disruptions, including increased triglycerides and altered lipoprotein composition. Despite milder clinical respiratory symptoms, children's metabolic disturbances mirrored those seen in severe adult COVID-19 patients, indicating a shared inflammatory response to SARS-CoV-2. This suggests potential long-term health impacts, underscoring the need for continued research into the metabolic consequences of COVID-19 in children.

Type 2 diabetes mellitus (T2DM) is a common metabolic disorder characterized by chronic hyperglycaemia, with physical inactivity and excessive adiposity as predisposing factors. This clinical trial aimed to investigate the effects of an exercise intervention on the metabolome of T2DM participants, fasting and in response to an oral glucose tolerance test (OGTT) and an acute exercise stimulus. Thirteen people with T2DM (age 51 ± 7 years; body mass index 32.7 ± 4.9 kg/m2) completed 45 min of moderate-intensity treadmill exercise on 12 days consecutively. Blood samples were collected before and after the first and last training sessions and during a pre- and postintervention OGTT. Fasted blood samples were collected from 198 healthy control subjects and 208 people with T2DM from an independent cohort for comparison. Samples were analysed using high-resolution 1H nuclear magnetic resonance spectroscopy and liquid chromatography–mass spectrometry. The exercise intervention did not induce a shift towards a healthier fasted metabolome in people living with T2DM. In response to consumption of a glucose bolus (OGTT), glycolysis-related metabolites increased and free fatty acids decreased, with no effect of the exercise intervention. In response to acute exercise, glucose and amino acids decreased and free fatty acids increased, with similar responses on the last day of training as on the first day, indicating no effect of the intervention. The clinical trial was registered prospectively in the Australian New Zealand Clinical Trials Registry ACTRN12617000286347 on 24 February 2017.

"NmrControlsDiabetesFasted" is a quantified 1H NMR dataset of 198 healthy controls, 208 people with type 2 diabetes mellitus (T2DM) who acted as disease controls, and 13 people with T2DM who participated in a twelve-day exercise intervention. Blood samples were collected cross-sectionally for healthy controls and T2DM-controls, whereas data from two time points (i.e., pre- and post-intervention) are provided for T2DM participants of the exercise intervention. All samples in this dataset were collected in a fasted state.

"NmrLipidsDiabetes" is a dataset of 13 people with T2DM who participated in a twelve-day exercise intervention. As part of the study, participants completed an oral glucose tolerance test (OGTT) before (OGTT1) and after (OGTT2) the twelve-day intervention. Fasted blood samples were collected prior to consuming a drink containing 75g of glucose and at 30-minute intervals until reaching the two-hour mark (i.e., at 30, 60, 90, and 120 minutes post-consumption). Additionally, blood samples were collected before (Pre) and immediately after (Post) exercise training on the first (Ex1) and last day (Ex12) of the intervention. Samples around the exercise sessions were only collected for nine participants. The OGTT and exercise samples were analysed using 1H NMR and lipidomics LC-MS methods.

NMR data were collected on Bruker 600 MHz Avance III HD spectrometers equipped with a BBI probe and with integral Bruker SampleJet robots, and data were automatically processed using Bruker Topspin™ 3.6.2 and ICON NMR to enable phasing, baseline correction, and calibration to TSP (δ = 0) (Dona et al., 2014; Lodge et al., 2021; Lodge et al., 2024).

Liquid chromatography was performed by a SCIEX ExionLC (SCIEX, Concord, CA) where separation was conducted using Waters Acquity BEH C18 1.7 μm, 2.1 × 100 mm column (Waters Corp., MA, USA) at 60°C (Ryan et al., 2023). Mass detection was conducted by a SCIEX QTRAP 6500+ (SCIEX, Concord, CA) with electrospray ionisation and polarity switching (Ryan et al., 2023).

Demographics of the study population and a detailed description of sample preparation and analysis are provided in the journal article associated with this dataset. A reference to this paper will be provided upon publication.

To investigate the acute effects of hypoxia applied during discrete work and recovery phases of a perceptually regulated, high-intensity interval exercise (HIIE) on external and internal loads in inactive overweight individuals. On separate days, 18 inactive overweight (28.7 ± 3.3 kg m−2; 31 ± 8 years) men and women completed a cycling HIIE protocol (6 × 1 min intervals with 4 min active recovery, maintaining a perceived rating of exertion of 16 and 10 during work and recovery, respectively, on the 6–20 Borg scale) in randomized conditions: normoxia (NN), normobaric hypoxia (inspired O2 fraction ∼0.14) during both work and recovery (HH), hypoxia during recovery (NH) and hypoxia during work only (HN). Markers of external (relative mean power output, MPO) and internal load (blood lactate concentration, heart rate and tissue saturation index (TSI)) were measured. MPO was lower in HH compared to NN, NH and HN (all P < 0.001), with HN also being lower than NN (P < 0.001) and NH (P < 0.023). Heart rate was higher in HN than NN, HH and NH (all P < 0.001). Blood lactate response was higher in NN than HH (P = 0.003) and NH (P = 0.008). Changes in the TSI area above the curve were greater in HN relative to NN, HH and NH (all P < 0.001). Hypoxia applied intermittently during the work or recovery phases may mitigate the declines in mechanical output observed when exercise is performed in continuous hypoxia, although hypoxia implemented during the work phase resulted in elevated heart rate and lactate response. Specifically, exercise performance largely comparable to that in normoxia can be achieved when hypoxia is implemented exclusively during recovery.

Dried blood spot (DBS) sample collections can offer a minimally invasive, cost-effective alternative to traditional venepuncture for remote sampling and high-frequency metabolic profiling. We present an optimised protocol for DBS-based extraction and comprehensive untargeted 4D lipid profiling using ultrahigh-performance liquid chromatography coupled with high-resolution mass spectrometry, designed to support large-scale applications in population-wide lipidomics research. Inclusion of stable isotopically labelled internal standards allowed for semi-quantitative subclass-level correction for 10 μL DBS samples, enhancing the number of reproducible lipids within our curated target list (focussed on 432 unique rule-based lipid annotations out of 6845 features) across positive and negative heated electrospray ionisation modes. The reproducibility of unique lipid features detected in replicate DBS (n = 6) was assessed on both peak areas (351 lipids < 25 % CV) and calculated concentrations relative to internal standards (432 lipids < 25 % CV), underscoring the benefit of internal standard addition. Storage conditions for DBS were also evaluated to determine short-term lipid stability at different temperatures (-20 ˚C, 4 ˚C, room temperature, and 45 ˚C). The majority of lipid subclasses, excluding a minority of glycerophospholipids and oxylipins, were stable up to 1 week at -20 ˚C and 4 ˚C (log2-fold change < 30 % difference), which supports the short-term storage capacity for DBS in field and clinical settings. Similar stability was observed within a week at room temperature, excluding phosphatidylethanolamines and phosphatidylglycerols (log2-fold change > 30 % difference). Application of the optimised workflow to a microsampling device (n = 6) identified 432 lipid features (CV < 25 %) with three repeated samplings over an hour showing minimal impact on lipid profiles by principal component analysis, showing promise for high-frequency, longitudinal DBS monitoring in population health. This work represents a significant advance, highlighting the potential for reliable lipid analysis from DBS samples with short-term stability under various storage conditions, an important logistical benefit for remote or resource-limited settings.
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•Dried blood spots enable minimally invasive, cost-effective sampling in lipidomics•The developed untargeted 4D-lipidomic method annotates 432 lipids in 10 μL DBS•Majority of lipid subclasses are stable on DBS up to 1 week, ideal at -20°C and 4°C•Commercial microsampling devices suit remote, high-frequency lipid profiling

We investigated plasma and serum blood derivatives from capillary blood microsamples (500 μL, MiniCollect tubes) and corresponding venous blood (10 mL vacutainers). Samples from 20 healthy participants were analyzed by 1 H NMR, and 112 lipoprotein subfraction parameters; 3 supramolecular phospholipid composite (SPC) parameters from SPC 1 , SPC 2 , and SPC 3 subfractions; 2 N-acetyl signals from α-1-acid glycoprotein (Glyc), GlycA, and GlycB; and 3 calculated parameters, SPC (total), SPC 3 /SPC 2 , and Glyc (total) were assessed. Using linear regression between capillary and venous collection sites, we explained that agreement (Adj. R 2 ≥ 0.8, p < 0.001) was witnessed for 86% of plasma parameters (103/120) and 88% of serum parameters (106/120), indicating that capillary lipoprotein, SPC, and Glyc concentrations follow changes in venous concentrations. These results indicate that capillary blood microsamples are suitable for sampling in remote areas and for high-frequency longitudinal sampling of the majority of lipoproteins, SPCs, and Glycs.

To ensure biological validity in metabolic phenotyping, findings must be replicated in independent sample sets. Targeted workflows have long been heralded as ideal platforms for such validation due to their robust quantitative capability. We evaluated the capability of liquid chromatography-mass spectrometry (LC-MS) assays targeting organic acids and bile acids to validate metabolic phenotypes of SARS-CoV-2 infection. Two independent sample sets were collected: (1) Australia: plasma, SARS-CoV-2 positive (
= 20), noninfected healthy controls (
= 22) and COVID-19 disease-like symptoms but negative for SARS-CoV-2 infection (
= 22). (2) Spain: serum, SARS-CoV-2 positive (
= 33) and noninfected healthy controls (
= 39). Multivariate modeling using orthogonal projections to latent structures discriminant analyses (OPLS-DA) classified healthy controls from SARS-CoV-2 positive (Australia;
= 0.17, ROC-AUC = 1; Spain
= 0.20, ROC-AUC = 1). Univariate analyses revealed 23 significantly different (
< 0.05) metabolites between healthy controls and SARS-CoV-2 positive individuals across both cohorts. Significant metabolites revealed consistent perturbations in cellular energy metabolism (pyruvic acid, and 2-oxoglutaric acid), oxidative stress (lactic acid, 2-hydroxybutyric acid), hypoxia (2-hydroxyglutaric acid, 5-aminolevulinic acid), liver activity (primary bile acids), and host-gut microbial cometabolism (hippuric acid, phenylpropionic acid, indole-3-propionic acid). These data support targeted LC-MS metabolic phenotyping workflows for biological validation in independent sample sets.

We present compelling evidence for the existence of an extended innate viperin-dependent pathway, which provides crucial evidence for an adaptive response to viral agents, such as SARS-CoV-2. We show the in vivo biosynthesis of a family of novel endogenous cytosine metabolites with potential antiviral activities. Two-dimensional nuclear magnetic resonance (NMR) spectroscopy revealed a characteristic spin-system motif, indicating the presence of an extended panel of urinary metabolites during the acute viral replication phase. Mass spectrometry additionally enabled the characterization and quantification of the most abundant serum metabolites, showing the potential diagnostic value of the compounds for viral infections. In total, we unveiled ten nucleoside (cytosine- and uracil-based) analogue structures, eight of which were previously unknown in humans allowing us to propose a new extended viperin pathway for the innate production of antiviral compounds. The molecular structures of the nucleoside analogues and their correlation with an array of serum cytokines, including IFN-α2, IFN-γ, and IL-10, suggest an association with the viperin enzyme contributing to an ancient endogenous innate immune defense mechanism against viral infection.

Objectives
To map and summarise the sports coaches’ and support staff's perspectives on athlete monitoring to explore the breadth of literature, identify knowledge gaps and inform future research.

Design
Scoping review based on the Joanna Briggs Institute (JBI) methodology.

Methods
SPORTDiscus, MEDLINE, APA PsycInfo, and Embase databases were searched in English until 6 September 2022. The inclusion criteria were (1) coach(es) and/or support staff were explicitly questioned about their knowledge, perceptions, understanding, opinions, and/or applied practice of athlete monitoring; (2) results could be directly attributed to coach(es) and/or support staff; (3) primary research projects that are available as full-text. Exclusion criteria were applied for grey literature. The data were extracted into a custom-made data charting spreadsheet.

Results
From the 4381 identified records, 42 met the eligibility criteria. Almost all the studies were conducted within the Anglosphere and at the national or international level. The main reasons for coaches and support staff to implement athlete monitoring were to reduce injury and illness, inform the training program, and improve or maintain performance. While training load monitoring is generally seen as valuable the coaches and support staff acknowledged that there was no perfect scientific approach to monitoring athletes and believed it should be part of the bigger picture, emphasising communication.

Conclusions
There has been a recent surge in research demonstrating that athlete monitoring extends beyond quantitative information and encompasses non-quantified subjective information. This further substantiates that coaches and support staff will remain central to athlete monitoring, even amidst the anticipated technological progress.