Stabilizing the Proteomes of Acute Myeloid Leukemia Cells: Implications for Cancer Proteomics.

Previous work has shown that inhibition of abundant myeloid azurophil granule-associated serine proteases (ELANE [neutrophil elastase], PRTN3 [protease 3], and CTSG [Cathepsin G]) is required to stabilize some proteins in myeloid cells. We therefore hypothesized that effective inhibition of these proteases may be necessary for quantitative proteomic analysis of samples containing myeloid cells. To test this hypothesis, we thawed viably preserved acute myeloid leukemia cells from cryovials in the presence or the absence of diisopropyl fluorophosphate (DFP), a cell-permeable and irreversible serine protease inhibitor. Global proteomic analysis was performed, using label-free and isobaric peptide-labeling quantitation. The presence of DFP resulted in an increase of tryptic peptides (14-57%) and proteins (9-31%). In the absence of DFP, 11 to 31% of peptide intensity came from nontryptic peptides; 52 to 75% had cleavage specificity consistent with activities of ELANE-PRTN3. Treatment with DFP reduced the intensity of nontryptic peptides to 4-8% of the total. ELANE inhibition was 95%, based on diisopropyl phosphate modification of active site serine residue. Overall, the relative abundance of 20% of proteins was significantly altered by DFP treatment. These results suggest that active myeloid serine proteases, released during sample processing, can skew quantitative proteomic measurements. Finally, significant ELANE activity was also detected in Clinical Proteomics Tumor Analysis Consortium datasets of solid tumors (many of which have known myeloid infiltration). In the pancreatic cancer dataset, the median percentage of nontryptic intensity detected across patient samples was 34%, with many patient samples having more than half of their detected peptide intensity from nontryptic cleavage events consistent with ELANE-PRTN3 cleavage specificity. Our study suggests that in vitro cleavage of proteins by myeloid serine proteases may be relevant for proteomic studies of any tumor that contains infiltrating myeloid cells.

Multifocal primary intrapulmonary thymoma successfully resected via robotic-assisted thoracoscopic surgery.

Primary intrapulmonary thymoma (PIT) represents a rare subset of ectopic thymoma that arises solely from inside the pulmonary parenchyma. Multifocal PIT, where multiple isolated PIT origins coexist in the lungs, has only been confirmed in one previous case report, in which the patient died before surgical resection. These tumours are difficult to diagnose as imaging findings are non-specific, and non-invasive biopsy often yields inaccurate results. We present the case of a man in his 70s who was referred to thoracic surgery for resection of a presumptive endobronchial pulmonary carcinoid tumour. Only after surgical resection did we identify that the patient had multifocal PIT. In this report, we describe our diagnostic and management process for this patient and review the current literature on PIT.

First Real-World Experience With Bigfoot Unity: A 6-Month Retrospective Analysis.

The Bigfoot Unity Diabetes Management System, a smart pen cap system cleared by the U.S. Food and Drug Administration in May 2021, incorporates continuous glucose monitoring data, real-time glycemic alerts, and clinician-directed dose recommendations. This study analyzed real-world clinical outcomes data for an initial cohort (n = 58, from 13 clinics) managing multiple daily injection insulin therapy using the pen cap system for 6 months. We examined glycemic control, including hypoglycemia events and interaction with and use of the pen cap system. In a cohort mainly consisting of adults with type 2 diabetes and an average age of 62 years, the results demonstrate close adherence to established glycemic targets, including a relatively short amount of time spent in the hypoglycemic range.

Medium chain triglycerides with a C8:C10 ratio of 30:70 enhances cognitive performance and mitigates the cognitive decline associated with prolonged exercise in young and healthy adults.

INTRODUCTION: Prolonged exercise has been linked to a decline in cognitive function due to a variety of factors, such as a drop in oxygen in the prefrontal cortex and an increase in stress hormones and neurotransmitters. Medium chain triglycerides (MCTs) may possibly offset this decline as they provide energy for the brain via both direct and indirect pathways, alongside promoting chronic physiological adaptations within the brain. METHODS: Participants were divided into two groups; MCT (n = 9) and Placebo (n = 10). The MCT gels contained 6 g of MCT with a C8:C10 ratio of 30:70, whereas the placebo gels contained carbohydrates of similar calorific value to the MCT gels. Participants visited the laboratory on three occasions (familiarisation/fitness test, pre-supplementation, post-supplementation), during which they performed a battery of cognitive tasks assessing domains such as processing speed, working memory, selective attention, decision making and coordination, before and after a prolonged bout of exercise (60 mins at 90% gas exchange threshold (GET). A 2-week supplementation period between visits 2 and 3 involved the ingestion of 2 gels per day. RESULTS: Exercise resulted in detriments in most cognitive tasks pre-supplementation for both groups, and post-supplementation for the Placebo group (main effect ps< 0.05). Post-supplementation, the effect of exercise was mediated in the MCT group for all cognitive tasks (main effect ps< 0.05), except for the Digit and Spatial Span Backwards test phases (main effect ps> 0.05). Furthermore, MCT supplementation enhanced before-exercise cognitive performance and in some measures, such as working memory, this was maintained after-exercise (interaction effect ps> 0.05). CONCLUSIONS: Chronic MCT supplementation enhanced before-exercise cognitive performance and offset the cognitive decline caused by a prolonged bout of exercise. In some cases, improvements in before-exercise cognitive performance were maintained after-exercise.

Intra-unit reliability and movement variability of submission grappling external load as measured by torso mounted accelerometery.

Submission grappling consists of skills and movements used in combat sports to physically control opponents whilst trying to apply choke holds and joint locks. There is currently no accepted method of monitoring external load in grappling-based sports due to the absence of key variables such as distance, velocity or time. The primary aim of this study was to determine whether PlayerLoad is a reliable variable for measuring external load of submission grappling movements, with a secondary aim of determining the between repetition variance of submission grappling movements. 7 experienced submission grapplers were recruited. Each wore a torso mounted Catapult® Optimeye S5 microelectromechanical systems (MEMS) device and completed 5 repetitions of each of the following: 4 submission techniques; 5 transition techniques; 2 guard pass techniques; 2 takedown techniques. Accumulated PlayerLoad (PLdACC) was recorded as a marker of absolute load, with accumulated PlayerLoad per minute (PLdACC∙min-1) representing relative load. Reliability of each was assessed using intraclass correlation coefficient (ICC(3,1)) (≥ 0.70). Between repetition movement variation was assessed via coefficient of variation with 95% confidence intervals (CV, 95%CI) (acceptable ≤ 15%, good ≤ 10%). PLdACC ICC(3,1) range = 0.78-0.98, with CV range = 9-22%. PLdACC∙min-1 ICC(3,1) range = 0.83-0.98, with CV range = 11-19%. Though several variables displayed CV > 15%, all had 95%CI lower boundaries ≤ 15%. Whilst PlayerLoad was found to be a reliable measure for submission grappling, relatively high CVs across most techniques examined suggest PlayerLoad may not be appropriate for measuring changes in external load for individual movements in submission grappling. However, it may prove a useful tool for monitoring the external load of full, grappling-based, training sessions within an individual.

The influence of physical performance on technical and tactical outcomes in the UEFA Champions League.

BACKGROUND: To clarify does physical performance affect success in highest-level soccer, the purpose of the present study was to identify differences in technical-tactical performance (TP) between teams covering high and low running performance (RP) during the UEFA Champions League (UCL) matches. METHODS: The RP and TP data were collected from UCL group stage matches in the 2020/21 season. RP variables included total distance covered (TD), high intensity running (HIR), total distance when in ball possession (TDB), and high intensity running when in ball possession (HIRB). TP variables included goal chances, shots, shots on target, passes, accurate passes, key passes, key passes accurate, crosses, crosses accurate, counter attacks, counter attacks with a shot, high pressing, high pressing successful, low pressing, low pressing successful, tackles, tackles successful, entrances to the opponent's box, total actions, and successful actions. K-means cluster analysis method was used to classify teams covering (i) low and high TD, (ii) low and high HIR, (iii) low and high TDB, (iv) low and high and HIRB. Linear mixed models were used to identify differences in teams' TP according to their RP. Pearson's correlations were used to establish direct association between team TP and RP. RESULTS: Similar TP were observed whether teams covering high or low TD/HIR. Teams covering greater TDB/HIRB had more goal chances, shots, shots on target, passes, accurate passes, key passes, accurate key passes, crosses, successful high pressing, entrances to the opponent's box, total actions, and successful actions were observed (all moderate to very large effect sizes. Significant association between specific TP variables and TDB/HIRB were evidenced (Pearson's r = 0.35-0.96, all p < 0.05). CONCLUSION: Covering greater TDB and HIRB may allow more frequent execution of fundamental TP which are considered essential for match success, indicating that RP when team has ball in possession is important determinant of success in highest-level soccer. This study shows that physical performance affect success in highest-level soccer.

A Simple Standard for Sharing Ontological Mappings (SSSOM).

Despite progress in the development of standards for describing and exchanging scientific information, the lack of easy-to-use standards for mapping between different representations of the same or similar objects in different databases poses a major impediment to data integration and interoperability. Mappings often lack the metadata needed to be correctly interpreted and applied. For example, are two terms equivalent or merely related? Are they narrow or broad matches? Or are they associated in some other way? Such relationships between the mapped terms are often not documented, which leads to incorrect assumptions and makes them hard to use in scenarios that require a high degree of precision (such as diagnostics or risk prediction). Furthermore, the lack of descriptions of how mappings were done makes it hard to combine and reconcile mappings, particularly curated and automated ones. We have developed the Simple Standard for Sharing Ontological Mappings (SSSOM) which addresses these problems by: (i) Introducing a machine-readable and extensible vocabulary to describe metadata that makes imprecision, inaccuracy and incompleteness in mappings explicit. (ii) Defining an easy-to-use simple table-based format that can be integrated into existing data science pipelines without the need to parse or query ontologies, and that integrates seamlessly with Linked Data principles. (iii) Implementing open and community-driven collaborative workflows that are designed to evolve the standard continuously to address changing requirements and mapping practices. (iv) Providing reference tools and software libraries for working with the standard. In this paper, we present the SSSOM standard, describe several use cases in detail and survey some of the existing work on standardizing the exchange of mappings, with the goal of making mappings Findable, Accessible, Interoperable and Reusable (FAIR). The SSSOM specification can be found at http://w3id.org/sssom/spec. Database URL: http://w3id.org/sssom/spec.

Energy Requirements and Nutritional Strategies for Male Soccer Players: A Review and Suggestions for Practice.

Soccer is a high intensity intermittent sport, featuring critical events completed at high/maximal intensity which is superimposed onto an aerobic base of lower intensity activities and rest. Due to these varying energic demands and the duration of competition the need for optimal nutritional strategies to offset and delay fatigue are paramount. Over the last 50 years, several investigations have been reported on aspects of soccer be they nutrition-focused or those concerning the demands of the sport. Emanating from these scientific papers, observations have been made on the likely factors which result in the fatigue during match-play. Factors such as muscle glycogen depletion and hypoglycaemia are discussed. Studies on the energy demands of soccer have employed a variety of methodologies which are briefly reviewed and vary between the use of heart rate telemetry to the use of global positioning systems (GPS). Moving on from observations of the energy demands of the sport leads to the major focus of this review which highlights key nutritional strategies to support the preparation and recovery of male soccer players to enhance performance, or at least to enable players to perform adequately. This review examines relevant methodologies in assessing training and competitive energy costs as well as the concomitant energy intakes demanded for successful performance outcomes. In order to bring an applied aspect to the overall findings from areas discussed, some practical ideas of feeding strategies are presented.

Interchangeability of player movement variables from different athlete tracking systems in professional soccer.

This study assessed the interchangeability between 10-Hz multi-GNSS GPS devices (Vector®) and two optical tracking systems (TRACAB® and Second Spectrum®). The agreement between data from the optical tracking systems when processed with manufacturer and GPS-filtered software was also assessed. Thirty players competing in the English Premier League were monitored using three different tracking systems across five matches. To determine the interchangeability between systems, player movement variables including, total distance, high-speed running distance (19.8-25.2 km·h-1), sprinting distance (>25.2 km·h-1), efforts >19.8 km·h-1 and maximal speed were compared. Equations were formed using linear regression and linear mixed-effects models to allow interchangeability of player movement variables between systems. Over half of the variance of most interchangeability equations were explained and associated with very strong positive correlations (r > 0.72). Small to huge differences were found between systems for most player movement variables. Data of optical tracking systems had decreased values in speed variables >19.8 km·h-1 when processed through GPS software. This study provides equations for practitioners to interchange player movement variables between TRACAB, Second Spectrum and Vector GPS systems with reduced error. This will enable practitioners to combine and share data captured with different tracking systems to analyse and improve their training.

Cold for centuries: a brief history of cryotherapies to improve health, injury and post-exercise recovery.

For centuries, cold temperatures have been used by humans for therapeutic, health and sporting recovery purposes. This application of cold for therapeutic purposes is regularly referred to as cryotherapy. Cryotherapies including ice, cold-water and cold air have been popularised by an ability to remove heat, reduce core and tissue temperatures, and alter blood flow in humans. The resulting downstream effects upon human physiologies providing benefits that include a reduced perception of pain, or analgesia, and an improved sensation of well-being. Ultimately, such benefits have been translated into therapies that may assist in improving post-exercise recovery, with further investigations assessing the role that cryotherapies can play in attenuating the ensuing post-exercise inflammatory response. Whilst considerable progress has been made in our understanding of the mechanistic changes associated with adopting cryotherapies, research focus tends to look towards the future rather than to the past. It has been suggested that this might be due to the notion of progress being defined as change over time from lower to higher states of knowledge. However, a historical perspective, studying a subject in light of its earliest phase and subsequent evolution, could help sharpen one's vision of the present; helping to generate new research questions as well as look at old questions in new ways. Therefore, the aim of this brief historical perspective is to highlight the origins of the many arms of this popular recovery and treatment technique, whilst further assessing the changing face of cryotherapy. We conclude by discussing what lies ahead in the future for cold-application techniques.

Effect of alterations in whole-body cryotherapy (WBC) exposure on post-match recovery markers in elite Premier League soccer players.

The use of whole-body cryotherapy (WBC) as a recovery intervention is prevalent amongst elite soccer players. However, there is a distinct lack of data available around chronic WBC use and post-match recovery markers in elite soccer. The aim of this study was to investigate the impact of different levels of WBC exposure on subjective and objective measures of post-match recovery in elite soccer players during a chronic exposure period. Sixteen male senior professional outfield soccer players participated in this study over two seasons. K means cluster analysis was used to classify low (-114 ± 2°C for 133 ± 2 s), medium (-121 ± 1°C for 173 ± 2 s) and high (-133 ± 1°C for 181 ± 2 s) cryotherapy exposure indexes (CEI). Salivary markers (immunoglobulin A (IgA) and alpha amylase (AA)) and subjective wellness scores (perceived fatigue, sleep quality, general muscle soreness and stress) were collected post-match across both seasons. Training load (session-RPE) was collected and used as a covariate to control for the load amongst groups. No differences were seen in perceived measures of wellness and salivary AA. Significantly lower IgA concentrations were observed in the medium CEI group (255 ± 32 µg∙ml-1) compared to the low (328 ± 38 µg∙ml-1) and high (306 ± 32 µg∙ml-1) groups. Therefore, increasing the level of chronic WBC exposure appears to have no additional benefit on subjective recovery and alpha amylase response post-match. However, there appears to be an optimal chronic WBC dose with regards to IgA response.

Exogenous carbohydrate and regulation of muscle carbohydrate utilisation during exercise.

PURPOSE: Carbohydrates (CHO) are one of the fundamental energy sources during prolonged steady state and intermittent exercise. The consumption of exogenous CHO during exercise is common place, with the aim to enhance sporting performance. Despite the popularity around exogenous CHO use, the process by which CHO is regulated from intake to its use in the working muscle is still not fully appreciated. Recent studies utilizing the hyperglycaemic glucose clamp technique have shed light on some of the potential barriers to CHO utilisation during exercise. The present review addresses the role of exogenous CHO utilisation during exercise, with a focus on potential mechanisms involved, from glucose uptake to glucose delivery and oxidation at the different stages of regulation. METHODS: Narrative review. RESULTS: A number of potential barriers were identified, including gastric emptying, intestinal absorption, blood flow (splanchnic and muscle), muscle uptake and oxidation. The relocation of glucose transporters plays a key role in the regulation of CHO, particularly in epithelial cells and subsequent transport into the blood. Limitations are also apparent when CHO is infused, particularly with regards to blood flow and uptake within the muscle. CONCLUSION: We highlight a number of potential barriers involved with the regulation of both ingested and infused CHO during exercise. Future work on the influence of longitudinal training within the regulation processes (such as the gut) is warranted to further understand the optimal type, dose and method of CHO delivery to enhance sporting performance.

The effects of medium chain triglyceride (MCT) supplementation using a C8:C10 ratio of 30:70 on cognitive performance in healthy young adults.

PURPOSE: The brain can utilise medium chain triglycerides (MCTs) as an alternative fuel to glucose, and research has shown that MCT ingestion improves cognitive function in diseased and/or elderly individuals. The aim of this study is to determine if these improvements can also be observed in young, healthy adults. Furthermore, we aim to establish the ideal dosage and timeframe necessary for an effect. METHODS: Participants were divided equally into three groups of 10 (Placebo (0 g), 12 g and 18 g MCT/day) and were supplemented for 4 weeks. The supplement had a C8:C10 ratio of 30:70. Participants visited the laboratory once a week for 5 weeks (baseline, test weeks 1-4) to undergo a battery of cognitive tests; Trail Making, Digit Span, Spatial Span, Covert Shift of Attention, and Rapid Visual Information Processing. RESULTS: After 2-3 weeks of supplementation, MCT ingestion enhanced performance in cognitive tasks, including: Trail Making A/B and Digit Span Forwards/Backwards (ps<0.001) when compared to a placebo group taking a carbohydrate gel. In Spatial Span Backwards, there was a significant main effect of group (p = 0.002). Where significance was seen, there were main effects of time after 2-3 weeks (ps<0.05). There was minimal difference between the two MCT intervention groups in most measures (ps>0.05). There were also null results in tasks measuring attention and reaction time (ps>0.05). CONCLUSIONS: MCT ingestion improved cognitive performance after 2-3 weeks, with minimal difference between taking 12 g and 18 g MCT/day groups, suggesting a possible dose-response threshold at 12 g MCT/day when supplementing over a short period.

Maturity-associated considerations for training load, injury risk, and physical performance in youth soccer: One size does not fit all.

Biological maturation can be defined as the timing and tempo of progress to achieving a mature state. The estimation of age of peak height velocity (PHV) or percentage of final estimated adult stature attainment (%EASA) is typically used to inform the training process in young athletes. In youth soccer, maturity-related changes in anthropometric and physical fitness characteristics are diverse among individuals, particularly around PHV. During this time, players are also at an increased risk of sustaining an overuse or growth-related injury. As a result, the implementation of training interventions can be challenging. The purpose of this review was to (1) highlight and discuss many of the methods that can be used to estimate maturation in the applied setting and (2) discuss the implications of manipulating training load around PHV on physical development and injury risk. We have provided key stakeholders with a practical online tool for estimating player maturation status (Supplementary Maturity Estimation Tools). Whilst estimating maturity using predictive equations is useful in guiding the training process, practitioners should be aware of its limitations. To increase the accuracy and usefulness of data, it is also vital that sports scientists implement reliable testing protocols at predetermined time-points.

Immediate effects of an acute bout of repeated soccer heading on cognitive performance.

Purpose: There isgrowing concern surrounding the harmful effects of soccer heading on cognitive function. The present study aims to examine the immediate effects of heading.Methods: 30 recreational male soccer players were divided into three groups that undertook 20 consecutive headers with a soft (8.8 psi), hard (16.2 psi), or no (control) ball. A battery of neuropsychological tests was completed before and after heading: King-Devick, trail-making (TM) (A, B), digit span (DS) and spatial span (SS) (forward, backward).Results: Significant increase in the time (M = 4.44 s) and errors (M = 1.45) for the King-Devick test within the hard and soft groups, although there was no significant difference for TM-A and TM-B. Significant decline for SS forward within the hard and soft groups (M= -16%), although the declines for SS backward (M = -16%), DS forward (M= -23%) and DS backward (M = -25%) were present only for the hard group (ps <.05).Discussion: While outside of regular match-play, this study showed that heading negatively influenced one indicator of a suspected concussion (King-Devick), as well as working memory (DS, SS) that is essential for daily life. These findings contribute to the growing debate surrounding heading safety.

A novel surgeon credentialing and quality assurance process using transoral surgery for oropharyngeal cancer in ECOG-ACRIN Cancer Research Group Trial E3311.

PURPOSE: Understanding the role of transoral surgery in oropharyngeal cancer (OPC) requires prospective, randomized multi-institutional data. Meticulous evaluation of surgeon expertise and surgical quality assurance (QA) will be critical to the validity of such trials. We describe a novel surgeon credentialing and QA process developed to support the ECOG-ACRIN Cancer Research Group E3311 (E3311) and report outcomes related to QA. PATIENTS AND METHODS: E3311 was a phase II randomized clinical trial of transoral surgery followed by low- or standard-dose, risk-adjusted post-operative therapy with stage III-IVa (AJCC 7th edition) HPV-associated OPC. In order to be credentialed to accrue to this trial, surgeons were required to demonstrate active hospital credentials and technique-specific surgical expertise with ≥20 cases of transoral resection for OPC. In addition, 10 paired operative and surgical pathology reports from the preceding 24 months were reviewed by an expert panel. Ongoing QA required <10% rate of positive margins, low oropharyngeal bleeding rates, and accrual of at least one patient per 12 months. Otherwise surgeons were placed on hold and not permitted to accrue until re-credentialed using a new series of transoral resections. RESULTS: 120 surgeons trained in transoral minimally invasive surgery applied for credentialing for E3311 and after peer-review, 87 (73%) were approved from 59 centers. During QA on E3311, positive final pathologic margins were reported in 19 (3.8%) patients. Grade III/IV and grade V oropharyngeal bleeding was reported in 29 (5.9%) and 1 (0.2%) of patients. CONCLUSIONS: We provide proof of concept that a comprehensive credentialing process can support multicenter transoral head and neck surgical oncology trials, with low incidence of positive margins and *grade III/V oropharyngeal bleeding.

A 3-day dietary manipulation affects muscle glycogen and results in modifications of carbohydrate and fat metabolism during exercise when hyperglycaemic.

PURPOSE: The effect of hyperglycaemia on exercise with low and elevated muscle glycogen on glucose utilization (GUR), carbohydrate and fat oxidation, hormonal and metabolite responses, as well as rating of perceived exertion (RPE) were explored. METHODS: Five healthy trained males were exercised for 90 min at 70% V̇O2max in two trials, while glucose was infused intravenously at rates to "clamp" blood glucose at 12 mM. On one occasion, participants were 'loaded' with carbohydrate (CHO-L), whilst on a separate occasion, participants were glycogen depleted (CHO-D). Prior exercise and dietary manipulations produced the 'loaded' and 'depleted' states. RESULTS: The CHO-L and CHO-D conditions resulted in muscle glycogen concentrations of 377 and 159 mmol/g dw, respectively. Hyperglycaemia elevated plasma insulin concentrations with higher levels for CHO-L than for CHO-D (P < 0.01). Conversely, CHO-D elevated plasma adrenaline and noradrenaline higher than CHO-L (P < 0.05). Plasma fat metabolites (NEFA, ß-hydroxybutyrate, and glycerol) were higher under CHO-D than CHO-L (P < 0.01). The resultant was that the rates of total carbohydrate and fat oxidation were elevated and depressed for loaded CHO-L vs CHO-D respectively (P < 0.01), although no difference was found for GUR (P > 0.05). The RPE over the exercise period was higher for CHO-D than CHO-L (P < 0.05). CONCLUSION: Hyperglycaemia during exercise, when muscle glycogen is reduced, attenuates insulin but promotes catecholamines and fat metabolites. The effect is a subsequent elevation of fat oxidation, a reduction in CHO oxidation without a concomitant increase in GUR, and an increase in RPE.