Factors That Impact Time to Athletic Trainer Evaluation Following Acute Injury Among Secondary School Athletes: A Report from the Athletic Trainin Practice-Based Research Network.

CONTEXT: Immediate athletic trainer (AT) availability for acute injuries is essential as worse long-term outcomes are associated with delays in receiving medical care. Several factors have been found to influence AT availability between secondary schools, but few studies have evaluated how medical coverage varies between athlete groups. OBJECTIVE: The purpose of this project was to identify factors that impact the time to AT evaluation following acute sport-related injury in secondary school setting. DESIGN: Cross-Sectional Study. SETTING: Retrospective analysis of de-identified patient records via the Athletic Training Practice-Based Research Network. PATIENTS: High school athletes diagnosed with an acute sport related injury during in-season play from 2010-2023. MAIN OUTCOME MEASURE: Time to AT evaluation was measured as the number of days between injury onset, reported by the patient, to AT evaluation. RESULTS: This report consists of 17,354 patient cases representing 20 different sports. Overall, 46.9% (n=8,138) of patients who sustained an injury during in-season play were evaluated by an AT the same day (range=0-14days). Significant group differences were reported for sex (p <. 001), setting (p <. 001), and sport level (p < .01), with females and in-game injuries associated with longer times to AT evaluation. Freshmen were evaluated sooner than JV (p < .01) and varsity (p < .001) athletes. No difference was observed between JV and varsity athletes (p=0.34). CONCLUSIONS: Almost half of patients received medical care within 24 hours following an acute injury during in-season play, highlighting how qualified health care is accessible for many student athletes through ATs in the secondary school setting. Differences in time to AT evaluation may be attributable to sex discrepancies in immediate medical coverage between sports and injury reporting patterns among athletes.

Secondary School Athletic Trainers' Perceptions of How Youth Sport Specialization Impacts Workload.

BACKGROUND: Youth sport specialization is a growing trend in youth sports and is associated with an increased risk of injuries and burnout. However, it is unknown how sport specialization is perceived to be affecting the working environment of secondary school athletic trainers (ATs). The purpose of this paper is to describe how ATs perceive youth sport specialization impacting their workload and whether they perceive it to impact patient safety. HYPOTHESIS: ATs will perceive that youth sport specialization impacts their workload and could impact patient safety. STUDY DESIGN: A sequential, explanatory mixed methods design with 2 phases: (1) cross-sectional surveys and (2) individual interviews. LEVEL OF EVIDENCE: Level 3. METHODS: A total of 487 secondary school ATs completed the online survey (access rate, 8.4%; completion rate, 85.4%). The survey consisted of Likert questions and included sections about aspects of workload impacted by specialization, impacts on patient safety, demographics. Ten participants were selected to complete a semi-structured interview via video conference. RESULTS: Approximately two-thirds of ATs perceive that sport specialization impacts their workload. (Somewhat, 38.6%; Quite a bit, 25.5%; A great deal, 5.5%) Attempts to reduce or modify patient activity and a patient's time for rehabilitation were the highest rated aspects of workload impacted by sport specialization. Approximately 30% ATs (29.9%) perceive that sport specialization impacts their workload to where it may influence patient safety (Somewhat, 21.6%; Quite a bit, 6.4%; A great deal, 1.9%). Three themes and subsequent subthemes were identified from the qualitative interviews: (1) current youth sport expectations, (2) conflict between school and club sports, and (3) AT job impacts. CONCLUSION: Secondary school ATs perceive their workload to be negatively impacted by youth sport specialization and some believe it may impact patient safety. CLINICAL RELEVANCE: Youth sport specialization is impacting youth sport stakeholders, including ATs, in a variety of ways.

Sport Specialization and Sport Motivation in Middle School-Aged Athletes.

CONTEXT: Sport specialization has been assumed to have psychosocial ramifications for athletes, especially autonomous motivation, which has been associated with continued sport participation. Sport dropout is common in youth athletes, yet it is unknown how sport specialization may affect this population psychosocially. OBJECTIVE: To determine the association of sport specialization with autonomous and controlled motivation and amotivation in middle school-aged athletes. DESIGN: Cross-sectional study. SETTING: An anonymous online questionnaire was distributed to athletes via schools, club sports, and social media. PATIENTS OR OTHER PARTICIPANTS: A total of 178 athletes (male = 59%; private school = 51%; grade: sixth = 20%, seventh = 32%, eighth = 48%) completed the questionnaire. MAIN OUTCOME MEASURE(S): The questionnaire assessed demographics, sport participation, and motivation using the Youth Behavioral Regulation in Sport Questionnaire. Sport specialization was defined using a modified 3-point scale (low, moderate, or high) and multisport versus single-sport athletes. Nonparametric tests were used to analyze the differences among the types of motivation and specialization levels and between multisport and single-sport athletes. RESULTS: Sport specialization categories were not significantly associated with autonomous motivation, controlled motivation, or amotivation. No significant associations were present between multisport or single-sport athletes and any type of motivation. However, multisport athletes had higher scores for intrinsic motivation, a subscale of autonomous motivation, compared with single-sport athletes (single sport: median = 5.00, 25th-75th quartile = 4.50-5.00; multisport: median = 5.00, 25th-75th quartile = 5.00-5.00; P = .04). CONCLUSIONS: Sport motivation did not differ between sport specialization groups in middle school athletes. Dropout from sport is common in this age group but is multifactorial in nature. A lack of sport motivation could be a factor for some athletes, but all specialization groups appeared to have similar outcomes. Our exploratory analysis suggests that clinicians may consider having an open dialogue with single-sport athletes, their parents or guardians, and coaches to ensure that athletes are enjoying their sport.

Motivation and Behaviors Related to Sport Specialization in College Baseball Players.

CONTEXT: Early sport specialization is a growing concern among youth sports athletes, particularly in baseball. Motivation to participate in sports is an important factor in determining which sports youth athletes participate in and why. OBJECTIVE: The purpose of this study was to qualitatively investigate youth sport participation behaviors and motivations of college baseball players. DESIGN: Qualitative Study. SETTING: Online Teleconference. PATIENTS OR OTHER PARTICIPANTS: We conducted 25 semi-structured interviews with college baseball athletes who were classified as either high-level (n=8), moderate-level (n=9), or low-level specialists (n=8) prior to college. DATA COLLECTION AND ANALYSIS: Participants completed an individual semi-structured interview to develop an understanding of the participants' youth and high school sports experiences and associated motivations to participate in those experiences. A framework analysis approach was used to analyze transcript data to identify themes among the three specialization groups. RESULTS: From our interview analysis, six overall themes emerged among the groups: (1) Motivation, (2) Stress, (3) Quitting, (4) Barriers, (5) Facilitators of Success, and (6) Future Directions. Moderate and high-level specialists described higher levels of passion, participating in deliberate practice, higher levels of performance-related stress, and a desire to quit sports more than low-level specialists. None of the groups described parents as an overbearing external motivator to participate in sports at an early age. CONCLUSIONS: Participants who were classified as low-, moderate-, and high-level specialists described different experiences related to their motivation, stress levels, desire to quit, barriers to participating in baseball, facilitators of success, and their overall future career goals after completing baseball. This information may be useful for parents, coaches, and health care professionals to better communicate the benefits and risks associated with sport specialization to youth athletes. Future research is needed to determine if differences in motivation levels exist in younger populations.

A mutagenesis study of autoantigen optimization for potential T1D vaccine design.

A previously reported autoreactive antigen, termed the X-idiotype, isolated from a unique cell population in Type 1 diabetes (T1D) patients, was found to stimulate their CD4+ T cells. This antigen was previously determined to bind more favorably than insulin and its mimic (insulin superagonist) to HLA-DQ8, supporting its strong role in CD4+ T cell activation. In this work, we probed HLA-X-idiotype-TCR binding and designed enhanced-reactive pHLA-TCR antigens using an in silico mutagenesis approach which we functionally validated by cell proliferation assays and flow cytometry. From a combination of single, double, and swap mutations, we identified antigen-binding sites p4 and p6 as potential mutation sites for HLA binding affinity enhancement. Site p6 is revealed to favor smaller but more hydrophobic residues than the native tyrosine, such as valine (Y6V) and isoleucine (Y6I), indicating a steric mechanism in binding affinity improvement. Meanwhile, site p4 methionine mutation to hydrophobic residues isoleucine (M4I) or leucine (M4L) modestly increases HLA binding affinity. Select p6 mutations to cysteine (Y6C) or isoleucine (Y6I) exhibit favorable TCR binding affinities, while a swap p5-p6 tyrosine-valine double mutant (V5Y_Y6V) and a p6-p7 glutamine-glutamine double mutant (Y6Q_Y7Q) exhibit enhanced HLA binding affinity but weakened TCR affinity. This work holds relevance to potential T1D antigen-based vaccine design and optimization.

Secondary School Athletic Trainers' Strategies and Barriers to Overuse Injury Treatment in Adolescent Athletes.

CONTEXT: Studies have illustrated that overuse injuries occur in adolescent athletes more often than previously reported. The general purpose of this study was to provide a thorough report of secondary school athletic trainers encounters, practices, and perceptions of overuse injury in adolescent athletes. DESIGN: Cross-sectional. METHODS: An anonymous online questionnaire was distributed via email to athletic trainers in the secondary school setting. The questionnaire was sent to participants during the summer of 2021 and 430 participants (highest educational degree earned: master's degree = 66%) completed the survey. Various survey methods were used to evaluate athletic trainers (1) demographics, (2) estimations about what percentage of injuries evaluated and treated were classified as overuse, (3) methods for treating overuse injuries, (4) confidence in treating overuse injuries and the complete implementation of their treatment plan, (5) perceptions of various barriers to treating overuse injuries, and (6) perception as to why patients did not want to reduce activity to treat their overuse injuries. RESULTS: Participants reported that about half of all evaluations and treatments in a year were overuse injuries and they were "fairly" or "completely" confident (90%) in their ability to treat these injuries. The most common treatments cited were stretching (91%) and reducing activity (90%). Only 61% of participants were "fairly" or "completely" confident in the complete implementation of their treatment plan. Participants believed that patients' reluctance to reduce sport activities (82% "moderate" or "extreme" barrier) was the most significant barrier to treatment. Participants cited athletes' avoidance of missing games as the most common reason athletes were reluctant to reduce sporting activity. CONCLUSIONS: Participants felt confident in treating overuse injuries yet faced significant barriers in treating these injuries. Clinicians should be prepared to have conversations about the importance of reducing sporting activity to allow proper healing for overuse injuries in adolescent athletes.

Impact of COVID-19 on the physical activity, quality of life and mental health of adolescent athletes: a 2-year evaluation of over 17 000 athletes.

PURPOSE: To evaluate the changes in mental health, quality of life (QOL) and physical activity (PA) among adolescent athletes during the COVID-19 pandemic as organised sports resumed. METHODS: Adolescent athletes completed surveys including demographic and sport participation information, 7-item Generalized Anxiety Disorder, 9-item Patient Health Questionnaire, Pediatric Quality of Life Inventory and the Hospital for Special Surgery Pediatric Functional Activity Brief Scale in May 2020 following COVID-19-related sport cancellations (Spring20) and after returning to sports in May 2021 (Spring21). The groups were balanced by inverse propensity score weighting and compared using analysis of variance models and ordinal regression models. RESULTS: 17 421 participants were included (Spring20=13 002; Spring21=4419; 16.2±1.2 years; 53% female). Anxiety was significantly lower (better) in Spring21 (Spring20=7.0, 95% CI 6.9 to 7.1; Spring21=4.9, 95% CI 4.8 to 5.0, p<0.001), as was the prevalence of moderate to severe anxiety (Spring20=29.4%, Spring21=17.1%, p<0.001). Depression was significantly improved in Spring21 (Spring20=7.6, 95% CI 7.5 to 7.7; Spring21=4.6, 95% CI 4.5 to 4.8, p<0.001), as was the prevalence of moderate to severe depression (Spring20=32.2%, Spring21=15.4%, p<0.001). Athletes in Spring21 reported higher QOL (Spring20=79.6, 95% CI 79.3 to 79.9; Spring21=84.7, 95% CI 84.4 to 85.0, p<0.001) and increased levels of PA (Spring20=13.8, 95% CI 13.6 to 13.9; Spring21=22.7, 95% CI 22.6 to 22.9, p<0.001). CONCLUSION: Early COVID-19 sports restrictions were associated with worsening mental health in adolescents. In 2021, after returning to sports, athletes reported significant improvements in mental health, QOL and PA, although mental health adversities remain an important priority.

A Multiyear Assessment of the Effect of Sport Participation on the Health of Adolescent Athletes During the COVID-19 Pandemic.

CONTEXT: Sport cancellations early in the COVID-19 pandemic had a significant negative effect on the health of US adolescents. The effect of restarting sports during the pandemic has not been described. OBJECTIVE: To identify the effect of sport participation on the health of adolescents before and during the COVID-19 pandemic. DESIGN: Cross-sectional study. SETTING: Sample recruited via social media. PATIENTS OR OTHER PARTICIPANTS: Wisconsin adolescent athletes. MAIN OUTCOME MEASURE(S): Participants provided information regarding their age, sex, and sport(s) involvement and completed the Patient Health Questionnaire-9 Item to assess depression symptoms, the Hospital for Special Surgery Pediatric Functional Activity Brief Scale to measure physical activity, and the Pediatric Quality of Life Inventory 4.0 to measure quality of life (QoL). Data were collected in spring 2021 (Spring21; n = 1906, age = 16.0 ± 1.2 years, females = 48.8%), when interscholastic sports had fully resumed, and were compared with similar cohorts of adolescent athletes at 2 time points: (1) spring 2020 (Spring20; n = 3243, age = 16.2 ± 1.2 years, females = 57.9%) when sports were cancelled and (2) 2016-2018 (PreCOVID-19) before the pandemic (n = 5231, age = 15.7 ± 1.1 years, females = 65.0%). Comparisons were conducted via analysis-of-variance models and ordinal regressions with age and sex as covariates. RESULTS: The prevalence of moderate to severe depression was lower in Spring21 than in Spring20 but higher than in PreCOVID-19 (PreCOVID-19 = 5.3%, Spring20 = 37.8%, Spring21 = 22.8%; P < .001). Physical activity scores (mean [95% CI]) were higher in Spring21 than in Spring20 but lower than in PreCOVID-19 (PreCOVID-19 = 23.1 [22.7, 23.5], Spring20 = 13.5 [13.3, 13.7], Spring21 = 21.9 [21.6, 22.2]). Similarly, QoL scores were higher in Spring21 than in Spring20 but lower than in PreCOVID-19 (PreCOVID-19 = 92.8 [92.5, 93.1], Spring20 = 80.7 [80.3, 81.1], Spring21 = 84.3 [83.8, 84.8]). CONCLUSIONS: Although sports have restarted, clinicians should be aware that physical activity, mental health, and QoL are still significantly affected in adolescent athletes by the ongoing pandemic.

Early Sport Specialization and Long-term Throwing Arm Health in College Baseball Players.

BACKGROUND: Early sport specialization is associated with increased risk of overuse injuries in several sports, including baseball. However, limited evidence exists evaluating how early sport specialization affects patient-reported outcome measures as they age. The purpose of this study was to determine differences in Kerlan-Jobe Orthopedic Clinic (KJOC) Shoulder and Elbow Scores among collegiate baseball players based on the grade when a participant first reported high specialization behaviors. HYPOTHESIS: Baseball players who were highly specialized at a younger age will have worse throwing arm health while participating in college. STUDY DESIGN: Cross-sectional study. LEVEL OF EVIDENCE: Level 3. METHODS: A total of 752 college baseball players was contacted through their institution's athletic trainer. We measured baseball specialization and KJOC scores using the validated Baseball and Sport Experience survey. Data were summarized using means and SDs, medians and interquartile ranges (IQRs), and frequencies and percentages. A Kruskal-Wallis test was used to determine differences in mean KJOC scale scores based on the earliest time the participant reported high-level specialization. RESULTS: A total of 294 baseball players completed the survey (response rate: 39.1%). Of the 294 participants, 280 completed the KJOC scale questions to generate a total KJOC score (median: 90.5; IQR: 76.6-97.2). No significant differences in KJOC total scores (P = 0.78) existed based on the grade period in which the athlete was first highly specialized. CONCLUSION: Early baseball specialization as a youth baseball player may not impact throwing arm health in college baseball athletes. CLINICAL RELEVANCE: Early specialization has been linked to increased risk for overuse injuries in certain sports, but may not lead to poorer throwing arm health in college baseball players. Sports medicine clinicians and researchers may use this information to educate various stakeholders about the benefits and risks associated with early sport specialization.

Epidemiology of Overuse Injuries in US Secondary School Athletics From 2014-2015 to 2018-2019 Using the National Athletic Treatment, Injury and Outcomes Network Surveillance Program.

CONTEXT: With 8 million annual US high school student-athletes, the epidemiology of sport-related injuries has garnered significant interest. The most recent studies examining overuse injury rates in high school sports were based on data from 2012 to 2013 and, therefore, may not reflect current overuse injury rates in high school sports. OBJECTIVE: To (1) determine overuse time-loss (TL) and non-time-loss (NTL) injury rates among high school student-athletes using National Athletic Treatment, Injury and Outcomes Network Surveillance Program (NATION-SP) data collected from 2014-2015 to 2018-2019 and (2) compare overuse injury rates based on student-athlete sex defined by whether it was a boys' sport or a girls' sport, the sport itself, and the injury location. DESIGN: Descriptive epidemiology study. SETTING: Online injury surveillance from 211 high schools (345 individual years of high school data). PATIENTS OR OTHER PARTICIPANTS: Athletes who participated in secondary school-sponsored boys' or girls' sports. MAIN OUTCOME MEASURE(S): Boys' and girls' overuse injury data from the NATION-SP during the 2014-2015 to 2018-2019 school years were analyzed. Overuse injuries were identified using a combination of the reported injury mechanism and diagnosis. Time-loss injuries resulted in restriction from participation beyond the day of injury; NTL injuries did not result in restriction from participation beyond the day of injury or involved no lost time due to the injury. Injury counts, rates, and rate ratios (IRRs) were reported with 95% CIs. RESULTS: The total overuse injury rate was 5.3/10 000 athlete-exposures (AEs; 95% CI = 5.1, 5.7), the NTL overuse injury rate was 3.4/10 000 AEs (95% CI = 3.1, 3.6), and the TL overuse injury rate was 2.0/10 000 AEs (95% CI = 1.8, 2.2). The overuse injury rate was greater in girls' sports compared with boys' sports (IRR = 1.9; 95% CI = 1.7, 2.1). The highest rates of overuse injury were observed in girls' cross-country (19.2/10 000 AEs; 95% CI = 15.0, 24.2), girls' track and field (16.0/10 000 AEs; 95% CI = 13.5, 18.8), and girls' field hockey (15.1/10 000 AEs; 95% CI = 10.2, 21.6). Overuse injury rates were higher for the lower extremity than the upper extremity (IRR = 5.7; 95% CI = 4.9, 6.7) and for the lower extremity than the trunk and spine (IRR = 8.9; 95% CI = 7.3, 10.8). CONCLUSIONS: Awareness of the overuse injury risk, as well as prevention and intervention recommendations, is necessary and should be specifically targeted at cross-country, field hockey, and track and field athletes.

Understanding interactions between biomolecules and two-dimensional nanomaterials using in silico microscopes.

Two-dimensional (2D) nanomaterials such as graphene are increasingly used in research and industry for various biomedical applications. Extensive experimental and theoretical studies have revealed that 2D nanomaterials are promising drug delivery vehicles, yet certain materials exhibit toxicity under biological conditions. So far, it is known that 2D nanomaterials possess strong adsorption propensities for biomolecules. To mitigate potential toxicity and retain favorable physical and chemical properties of 2D nanomaterials, it is necessary to explore the underlying mechanisms of interactions between biomolecules and nanomaterials for the subsequent design of biocompatible 2D nanomaterials for nanomedicine. The purpose of this review is to integrate experimental findings with theoretical observations and facilitate the study of 2D nanomaterial interaction with biomolecules at the molecular level. We discuss the current understanding and progress of 2D nanomaterial interaction with proteins, lipid membranes, and DNA based on molecular dynamics (MD) simulation. In this review, we focus on the 2D graphene nanosheet and briefly discuss other 2D nanomaterials. With the ever-growing computing power, we can image nanoscale processes using MD simulation that are otherwise not observable in experiment. We expect that molecular characterization of the complex behavior between 2D nanomaterials and biomolecules will help fulfill the goal of designing effective 2D nanomaterials as drug delivery platforms.

The Role of Athlete Competitiveness in High School Sport Specialization in the United States.

Background: Sport specialization has been associated with increased injury and negative psychosocial effects on young athletes. With the continuing trend toward specialization, studies have begun to examine what motivates this decision (eg, building a skill, getting a scholarship). No study has directly assessed the personal characteristics underlying these stated reasons. Purpose/Hypothesis: This study examined the role of athlete competitiveness (enjoyment of competition and competitive contentiousness) as a characteristic associated with propensity to specialize in the United States. We hypothesized that, at the high school level, athletes would be more likely to engage in sport specialization owing to enjoyment of competition versus competitive contentiousness. Study Design: Cross-sectional study; Level of evidence, 3. Methods: We conducted an online survey of 975 high school athletes in the United States who were recruited via the Dynata research panel. Measures included a previously published sport specialization categorization (low, medium, high) and the 2 dimensions of the Revised Competitiveness Index (enjoyment of competition and competitive contentiousness). Also collected were athlete characteristics, sports played by the athletes, level of competition, and whether they planned to play sports in college. Analytical methods employed included cross-tabulations, multinomial logit, and ordinary least squares regression. Results: Overall, 22.4% of the athletes reported a high, 34.8% reported a medium, and 42.9% reported a small level of specialization. No differences in the distribution of sport specialization by sex or age were observed; however, athletes who definitely planned to play in college were significantly more likely to have a high level of specialization (P < .001). Enjoyment of competition was associated with greater specialization (beta = .196; P < .001), whereas competitive contentiousness was associated with lower levels of specialization (beta = -.299; P < .001). These findings were robust to all 3 different analytical methods we employed. Conclusion: Study findings indicated that, while athlete competitiveness is associated with sport specialization, the nature of that competitiveness determined the association. Being an argumentative contrarian may predispose athletes to lower levels of sport specialization, whereas enjoying competition may encourage higher levels of specialization.

The Psychosocial Benefits of Sport Participation During COVID-19 Are Only Partially Explained by Increased Physical Activity.

The purpose of this study was to determine whether physical activity (PA) increases were responsible for the improvements in mental health and quality of life (QOL) seen among adolescents who returned to sport during the COVID-19 pandemic.Adolescent athletes were asked to complete a survey in October 2020 regarding demographic information, whether they had returned to sport participation (no [DNP], yes [PLY]), school instruction type (virtual, in-person, hybrid), anxiety, depression, QOL, and PA. Anxiety, depression, QOL and PA were compared between PLY and DNP using least squares means from linear models adjusted for age, gender, and instruction type. Mediation analysis assessed whether the relationship between sport status and anxiety, depression, and QOL was mediated by PA. 171 athletes had returned to play, while 388 had not. PLY athletes had significantly lower anxiety (3.6±0.4 v 8.2±0.6, p<0.001) and depression (4.2±0.4 v 7.3±0.6, p<0.001), and significantly higher QOL (88.1±1.0 v 80.2±1.4, p<0.001) and PA (24.0±0.5 v 16.3±0.7, p<0.001). PA explained a significant, but relatively small portion of the difference in depression (22.1%, p=0.02) and QOL (16.0%, p=0.048) between PLY and DNP athletes, but did not explain the difference in anxiety (6.6%, p=0.20). Increased PA is only responsible for a small portion of the improvements in depression and QOL among athletes who returned to sports and unrelated to improvements in anxiety. This suggests that the majority of the mental health benefits of sport participation for adolescents during the COVID-19 pandemic are independent of, and in addition to, the benefits of increased PA.

High School Sports During the COVID-19 Pandemic: The Effect of Sport Participation on the Health of Adolescents.

CONTEXT: During the fall of 2020, some high schools across the United States allowed their students to participate in interscholastic sports while others cancelled or postponed their sport programs due to concerns regarding COVID-19 transmission. What effect this has had on the physical and mental health of adolescents is unknown. OBJECTIVE: To identify the effect of playing a sport during the COVID-19 pandemic on the health of student-athletes. DESIGN: Cross-sectional study. SETTING: Sample recruited via email. PATIENTS OR OTHER PARTICIPANTS: A total of 559 Wisconsin high school athletes (age = 15.7 ± 1.2 years, female = 43.6%, male = 56.4%) from 44 high schools completed an online survey in October 2020. A total of 171 (30.6%) athletes played (PLY) a fall sport, while 388 (69.4%) did not play (DNP). MAIN OUTCOME MEASURE(S): Demographic data included sex, grade, and sport(s) played. Assessments were the General Anxiety Disorder-7 Item for anxiety, Patient Health Questionnaire-9 Item for depression, the Hospital for Special Surgery Pediatric Functional Activity Brief Scale for physical activity, and the Pediatric Quality of Life Inventory 4.0 for quality of life. Univariable comparisons between the 2 groups were made via t tests or χ2 tests. Means for each continuous outcome measure were compared between groups using analysis-of-variance models that controlled for age, sex, teaching method (virtual, hybrid, or in person), and the percentage of students eligible for free or reduced-price lunch. RESULTS: The PLY group participants were less likely to report moderate to severe symptoms of anxiety (PLY = 6.6%, DNP = 44.1%, P < .001) and depression (PLY = 18.2%, DNP = 40.4%, P < .001). They also demonstrated higher (better) Pediatric Functional Activity Brief Scale scores (PLY = 23.2 [95% CI = 22.0, 24.5], DNP = 16.4 [95% CI = 15.0, 17.8], P < .001) and higher (better) Pediatric Quality of Life Inventory total scores (PLY = 88.4 [95% CI = 85.9, 90.9], DNP = 79.6 [95% CI = 76.8, 82.4], P < .001). CONCLUSIONS: Adolescents who played a sport during the COVID-19 pandemic described fewer symptoms of anxiety and depression and had better physical activity and quality-of-life scores compared with adolescent athletes who did not play a sport.

Comparing High School Sport Specialization Trends Between Division I and Club Collegiate Athletes.

BACKGROUND: Adolescent athletes report that sports specialization improves their ability to receive a collegiate athletics scholarship, though this is not well-understood. The purpose of this study was to examine self-reported trends in high school specialization and influences for sport participation between Division I (D-I) and college-aged club (club) athletes. HYPOTHESIS: There would be no difference in high school sport specialization or sport participation influences between D-I and club athletes. STUDY DESIGN: Retrospective cross-sectional study. LEVEL OF EVIDENCE: Level 3. METHODS: A survey included specialization classification (low, moderate, and high) for 9th to 12th grade, age that the athlete started organized sport and his or her collegiate sport, and several influential factors for participation in one's primary high school sport (1 = no influence to 5 = extremely influential). Chi-square analyses were used to compare specialization classifications between groups. Nonparametric tests were used to determine significant differences in age-related variables and influential factors between D-I and club athletes. All analysis were also conducted with boys and girls separately. RESULTS: Participants included 266 D-I (girls, 155; 58%) and 180 club (girls, 122; 68%) athletes. Club athletes were more likely to be classified as low specialization at every grade in high school, and this difference was more pronounced between D-I and club female athletes than male athletes. The number of years an athlete was classified as highly specialized in high school was not different between D-I and club athletes. Club athletes were more influenced by playing with friends than D-I athletes and D-I athletes were more influenced by pursuing a collegiate scholarship than club athletes. CONCLUSION: High levels of specialization in high school sport may not be necessary for playing at the collegiate level, though some level of specialization in high school might be necessary. CLINICAL RELEVANCE: Clinicians should advocate for healthy long-term athlete development, which does not support high specialization in high school sports.

High School Sport Specialization and Injury in Collegiate Club-Sport Athletes.

CONTEXT: Sport specialization during adolescence may affect future injury risk. This association has been demonstrated in some professional sport athletes. OBJECTIVE: To determine the association between adolescent sport specialization levels in high school and injuries sustained during collegiate club sports. DESIGN: Cross-sectional study. SETTING: Paper and online surveys. PATIENTS OR OTHER PARTICIPANTS: Collegiate club-sport athletes. MAIN OUTCOME MEASURES(S): An anonymous survey was administered from September 2019 to May 2020. The survey included sport specialization classification via a commonly used 3-point scale (low, moderate, high) for each high school year (9th-12th), high school sports participation, and collegiate club-sport injury history. The number of years (0-4) an individual was highly specialized in high school was calculated. Individuals who participated in the same sport in high school and college were compared with individuals who played a different sport in college than in high school. An injury related to sport club activities was classified as arising from a contact, noncontact, or overuse mechanism required and the individual to seek medical treatment or diagnosis. Injuries were classified into overuse and acute mechanisms for the upper extremity, lower extremity (LE), and head/neck. RESULTS: Single-sport participation and the number of years highly specialized in high school sport were not associated with college club-sport injuries (P > .1). Individuals who played a different collegiate club sport than their high school sport were more likely to report an LE or head/neck acute injury compared with athletes who played the same collegiate and high school sport (LE = 20% versus 8%, χ2 = 7.4, P = .006; head/neck = 16% versus 3%, χ2 = 19.4, P < .001). CONCLUSIONS: Adolescent sport specialization was not associated with reported injuries in collegiate club-sport athletes. Collegiate club-sport athletic trainers should be aware that incoming students exploring a new sport may be at risk for LE and head/neck acute injuries.

Dynamics-Based Peptide-MHC Binding Optimization by a Convolutional Variational Autoencoder: A Use-Case Model for CASTELO.

An unsolved challenge in the development of antigen-specific immunotherapies is determining the optimal antigens to target. Comprehension of antigen-major histocompatibility complex (MHC) binding is paramount toward achieving this goal. Here, we apply CASTELO, a combined machine learning-molecular dynamics (ML-MD) approach, to identify per-residue antigen binding contributions and then design novel antigens of increased MHC-II binding affinity for a type 1 diabetes-implicated system. We build upon a small-molecule lead optimization algorithm by training a convolutional variational autoencoder (CVAE) on MD trajectories of 48 different systems across four antigens and four HLA serotypes. We develop several new machine learning metrics including a structure-based anchor residue classification model as well as cluster comparison scores. ML-MD predictions agree well with experimental binding results and free energy perturbation-predicted binding affinities. Moreover, ML-MD metrics are independent of traditional MD stability metrics such as contact area and root-mean-square fluctuations (RMSF), which do not reflect binding affinity data. Our work supports the role of structure-based deep learning techniques in antigen-specific immunotherapy design.

Evolution of Thyroglobulin Loop Kinetics in EpCAM.

Epithelial cell-activating molecule (EpCAM) is an important cancer biomarker and therapeutic target given its elevated expression in epithelial cancers. EpCAM is a type I transmembrane protein that forms cis-dimers along the thyroglobulin type-1A-like domain (TYD) in the extracellular region. The thyroglobulin loop (TY loop) within the TYD is structurally dynamic in the monomer state of human EpCAM, binding reversibly to a TYD site. However, it is not known if this flexibility is prevalent across different species. Here, we conduct over 17 µs of all-atom molecular dynamics simulations to study EpCAM TY loop kinetics of five different species, including human, mouse, chicken, frog, and fish. We find that the TY loop remains dynamic across evolution. In addition to the TYD binding site, we discover a second binding site for the TY loop in the C-terminal domain (CTD). Calculations of the dissociation rate constants from the simulation trajectories suggest a differential binding pattern of fish EpCAM and other organisms. Whereas fish TY loop has comparable binding for both TYD and CTD sites, the TY loops of other species preferably bind the TYD site. A hybrid construct of fish EpCAM with human TY loop restores the TYD binding preference, suggesting robust effects of the TY loop sequence on its dynamic behavior. Our findings provide insights into the structural dynamics of EpCAM and its implication in physiological functions.

Toward Guided Mutagenesis: Gaussian Process Regression Predicts MHC Class II Antigen Mutant Binding.

Antigen-specific immunotherapies (ASI) require successful loading and presentation of antigen peptides into the major histocompatibility complex (MHC) binding cleft. One route of ASI design is to mutate native antigens for either stronger or weaker binding interaction to MHC. Exploring all possible mutations is costly both experimentally and computationally. To reduce experimental and computational expense, here we investigate the minimal amount of prior data required to accurately predict the relative binding affinity of point mutations for peptide-MHC class II (pMHCII) binding. Using data from different residue subsets, we interpolate pMHCII mutant binding affinities by Gaussian process (GP) regression of residue volume and hydrophobicity. We apply GP regression to an experimental data set from the Immune Epitope Database, and theoretical data sets from NetMHCIIpan and Free Energy Perturbation calculations. We find that GP regression can predict binding affinities of nine neutral residues from a six-residue subset with an average R2 coefficient of determination value of 0.62 ± 0.04 (±95% CI), average error of 0.09 ± 0.01 kcal/mol (±95% CI), and with an receiver operating characteristic (ROC) AUC value of 0.92 for binary classification of enhanced or diminished binding affinity. Similarly, metrics increase to an R2 value of 0.69 ± 0.04, average error of 0.07 ± 0.01 kcal/mol, and an ROC AUC value of 0.94 for predicting seven neutral residues from an eight-residue subset. Our work finds that prediction is most accurate for neutral residues at anchor residue sites without register shift. This work holds relevance to predicting pMHCII binding and accelerating ASI design.

Changes in the Health of Adolescent Athletes: A Comparison of Health Measures Collected Before and During the COVID-19 Pandemic.

CONTEXT: In spring 2020, schools closed to in-person teaching and sports were cancelled to control the transmission of COVID-19. The changes that affected the physical and mental health among young athletes during this time remain unknown. OBJECTIVE: To identify changes in the health (mental health, physical activity, and quality of life) of athletes that occurred during the COVID-19 pandemic. DESIGN: Cross-sectional study. SETTING: Sample recruited via social media. PATIENTS OR OTHER PARTICIPANTS: A total of 3243 Wisconsin adolescent athletes (age = 16.2 ± 1.2 years, 58% female) were surveyed in May 2020 (During COVID-19). Measures for this cohort were compared with previously reported data for Wisconsin adolescent athletes (n = 5231; age = 15.7 ± 1.2 years, 47% female) collected in 2016 to 2018 (PreCOVID-19). MAIN OUTCOME MEASURE(S): Demographic information included sex, grade, and sport(s) played. Health assessments included the Patient Health Questionnaire-9 Item to identify depression symptoms, the Pediatric Functional Activity Brief Scale to gauge physical activity, and the Pediatric Quality of Life Inventory 4.0 to evaluate health-related quality of life. Univariable comparisons of these variables between groups were conducted via t or χ2 tests. Means and 95% CIs for each group were estimated using survey-weighted analysis-of-variance models. RESULTS: Compared with preCOVID-19 participants, a larger proportion of During COVID-19 participants reported moderate to severe levels of depression (9.7% versus 32.9%, P < .001). Scores of the During COVID-19 participants were 50% lower (worse) on the Pediatric Functional Activity Brief Scale (mean [95% CI] = 12.2 [11.9, 12.5] versus 24.7 [24.5, 24.9], P < .001) and the Pediatric Quality of Life Inventory 4.0 compared with the PreCOVID-19 participants (78.4 [78.0, 78.8] versus 90.9 [90.5, 91.3], P < .001). CONCLUSIONS: During the COVID-19 pandemic, adolescent athletes described increased symptoms of depression, decreased physical activity, and decreased quality of life compared with adolescent athletes in previous years.