Single-cell profiling reveals the importance of CXCL13/CXCR5 axis biology in lymphocyte-rich classic Hodgkin lymphoma.

Lymphocyte-rich classic Hodgkin lymphoma (LR-CHL) is a rare subtype of Hodgkin lymphoma. Recent technical advances have allowed for the characterization of specific cross-talk mechanisms between malignant Hodgkin Reed-Sternberg (HRS) cells and different normal immune cells in the tumor microenvironment (TME) of CHL. However, the TME of LR-CHL has not yet been characterized at single-cell resolution. Here, using single-cell RNA sequencing (scRNA-seq), we examined the immune cell profile of 8 cell suspension samples of LR-CHL in comparison to 20 samples of the mixed cellularity (MC, 9 cases) and nodular sclerosis (NS, 11 cases) subtypes of CHL, as well as 5 reactive lymph node controls. We also performed multicolor immunofluorescence (MC-IF) on tissue microarrays from the same patients and an independent validation cohort of 31 pretreatment LR-CHL samples. ScRNA-seq analysis identified a unique CD4+ helper T cell subset in LR-CHL characterized by high expression of Chemokine C-X-C motif ligand 13 (CXCL13) and PD-1. PD-1+CXCL13+ T cells were significantly enriched in LR-CHL compared to other CHL subtypes, and spatial analyses revealed that in 46% of the LR-CHL cases these cells formed rosettes surrounding HRS cells. MC-IF analysis revealed CXCR5+ normal B cells in close proximity to CXCL13+ T cells at significantly higher levels in LR-CHL. Moreover, the abundance of PD-1+CXCL13+ T cells in the TME was significantly associated with shorter progression-free survival in LR-CHL (P = 0.032). Taken together, our findings strongly suggest the pathogenic importance of the CXCL13/CXCR5 axis and PD-1+CXCL13+ T cells as a treatment target in LR-CHL.

Ultranarrow Line Width Room-Temperature Single-Photon Source from Perovskite Quantum Dot Embedded in Optical Microcavity.

Ultranarrow bandwidth single-photon sources operating at room-temperature are of vital importance for viable optical quantum technologies at scale, including quantum key distribution, cloud-based quantum information processing networks, and quantum metrology. Here we show a room-temperature ultranarrow bandwidth single-photon source generating single-mode photons at a rate of 5 MHz based on an inorganic CsPbI3 perovskite quantum dot embedded in a tunable open-access optical microcavity. When coupled to an optical cavity mode, the quantum dot room-temperature emission becomes single-mode, and the spectrum narrows down to just ∼1 nm. The low numerical aperture of the optical cavities enables efficient collection of high-purity single-mode single-photon emission at room-temperature, offering promising performance for photonic and quantum technology applications. We measure 94% pure single-photon emission in a single-mode under pulsed and continuous-wave (CW) excitation.

A Mixed-Methods Approach for Evaluating Implementation Processes and Program Costs for a Hypertension Management Program Implemented in a Federally Qualified Health Center.

Team-based care approaches are effective at improving hypertension control and have been used in clinical practice to improve hypertension outcomes. This study implemented and evaluated the Hypertension Management Program (HMP), which was originally developed in a high-resource health setting, in a health system with fewer resources and a patient population disproportionately affected by hypertension. Our objectives were to describe how a health system could adapt HMP to meet their needs and calculate total program costs. HMP uses a team-based, patient-centered approach involving clinical pharmacists who contribute to managing patients who have hypertension and ultimately preventing premature death due to uncontrolled hypertension. HMP has 10 components (e.g., EHR patient registries and outreach lists, no copayment walk-in blood pressure checks). Our project involved implementing the key components of HMP in a federally qualified health center (FQHC) in South Carolina. Adaptations from the key components of HMP were made to fit the participants' settings. A mixed-methods evaluation assessed implementation processes, program costs, and implementation facilitators and barriers. From September 2018 to December 2019, clinical pharmacists conducted 758 hypertension management visits (HMVs) with 316 patients with hypertension. Total program costs for HMP were $325,532 overall and $16,277 per month. Monthly cost per patient was $3.62. The high engagement among clinical pharmacists, along with provider engagements, followed up by the subsequent referral of patients to HMP, facilitated the implementation process. Staff members observed improvements in hypertension control, which increased participation buy-in. Barriers included staff turnover, the perception among some providers that HMP took too much time, as well as perception of HMP as a pharmacy-specific initiative. A team-based, patient-centered approach to hypertension management can be adapted for FQHCs or similar settings that serve patient populations disproportionately affected by hypertension.

Patients Experience Significant and Meaningful Changes in Self-Report of Function During the First 2 Weeks After an Ankle Sprain Injury: A Report From the Athletic Training Practice-Based Research Network.

CONTEXT: Ankle sprains are common during sport participation and associated with long-term deficits in self-report of function. However, little is known of short-term changes in self-report of function following injury. The authors aimed to assess statistical and clinically meaningful changes in self-report of function, as measured by the Foot and Ankle Ability Measure (FAAM), during the first 2 weeks after an ankle sprain injury. DESIGN: A retrospective analysis of electronic medical records. METHODS: Eighty-eight patients, who were diagnosed with an ankle sprain injury by an athletic trainer, received usual care from an athletic trainer, and completed the FAAM during treatment at weeks 1 and 2 postinjury. The authors calculated the percentage of patients who reported clinically meaningful changes and used Wilcoxon signed-rank tests to compare differences in FAAM scores between time points. RESULTS: Between weeks 1 and 2, significant differences were noted for the FAAM Activities of Daily Living (FAAM-ADL) (P < .001) and FAAM Sport (FAAM-Sport) (P < .001). At the patient level, 86.5% (64/74) and 85.2% (69/81) of patients reported changes that exceeded the minimal clinically important difference value for the FAAM-ADL and FAAM-Sport, respectively, between weeks 1 and 2. At week 2, 31.8% (28/88) and 47.7% (42/88) of patients reported a score below 90% on the FAAM-ADL and below 80% on the FAAM-Sport subscale, respectively. Also, 36.4% (32/88) and 25.0% (22/88) of patients reported a score of 100% on the FAAM-ADL and FAAM-Sport subscales, respectively, at week 2. CONCLUSIONS: Patients report statistically significant and meaningful improvements in self-report of function during the first 2 weeks following ankle sprain injury. However, almost half of patients still report deficits in sport function at 2 weeks postinjury. Patient-reported outcome measures such as the FAAM, can help capture the patient's perception of function and inform patient care decisions. Research efforts should explore individual response patterns to treatment.

Influence of Ligand Structure on Excited State Surface Chemistry of Lead Sulfide Quantum Dots.

The ligand-nanocrystal boundaries of colloidal quantum dots (QDs) mediate the primary energy and electron transfer processes that underpin photochemical and photocatalytic transformations at their surfaces. We use mid-infrared transient absorption spectroscopy to reveal the influence that ligand structure and bonding to nanocrystal surfaces have on the changes of the excited state surface chemistry of this boundary in PbS QDs and the corresponding impact on charge transfer processes between nanocrystals. We demonstrate that oleate ligands undergo marked changes in their bonding to surfaces in the excitonic excited states of the nanocrystals, indicating that oleate passivated PbS surfaces undergo significant structural changes following photoexcitation. These changes can impact the surface mobility of the ligands and the ability of redox shuttles to approach the nanocrystal surfaces to undergo charge transfer in photocatalytic reactions. In contrast, markedly different transient vibrational features are observed in iodide/mercaptoproprionic acid passivated PbS QD films that result from charge transfer between neighboring nanocrystals and localization of holes at the nanocrystal surfaces near MPA ligands. This ability to distinguish the influence that excitonic excited states vs charge transfer processes have on the surface chemistry of the ligand-nanocrystal boundary lays the groundwork for exploration of how this boundary can be understood and controlled for the design of nanocrystalline materials tailored for specific applications in solar energy harvesting and photocatalytic reactions.

The Impact of a Previous Ankle Injury on Current Health-Related Quality of Life in College Athletes.

CONTEXT: There has been an increased interest in understanding how ankle injuries impact patient outcomes; however, it is unknown how the severity of a previous ankle injury influences health-related quality of life (HRQOL). OBJECTIVE: To determine the impact of a previous ankle injury on current HRQOL in college athletes. DESIGN: Cross-sectional study. SETTING: Athletic training clinics. PARTICIPANTS: A total of 270 participants were grouped by the severity of a previous ankle injury (severe = 62, mild = 65, and no injury = 143). MAIN OUTCOME MEASURES: Participants completed the Foot and Ankle Ability Measure (FAAM) and the Short Form 12 (SF-12). METHODS: A 2-way analysis of variance with 2 factors (injury group and sex) was used to identify interaction and main effects for the FAAM and SF-12. RESULTS: No interactions were identified between injury group and sex. Significant main effects were observed for injury group, where the severe injury group scored lower than athletes with mild and no injuries on the FAAM activities of daily living, FAAM Global, and SF-12 mental health subscale scores. In addition, a main effect was present for sex in the SF-12 general health, social functioning, and mental health subscales in which females reported significantly lower scores than males. CONCLUSIONS: Our findings suggest that a severe ankle injury impacts HRQOL, even after returning back to full participation. In addition, females tended to report lower scores than males for aspects of the SF-12, suggesting that sex should be considered when evaluating HRQOL postinjury. As a result, clinicians should consider asking athletes about their previous injury history, including how much time was lost due to the injury, and should mindful of returning athletes to play before they are physiologically and psychologically ready, as there could be long-term negative effects on the patients' region-specific function as well as aspects of their HRQOL.

Pain Education With Therapeutic Exercise in Chronic Nonspecific Low Back Pain Rehabilitation: A Critically Appraised Topic.

Clinical Scenario: Low back pain is widely prevalent in the general population as well as in athletes. Therapeutic exercise is a low-risk and effective treatment option for chronic pain that can be utilized by all rehabilitation clinicians. However, therapeutic exercise alone does not address the psychosocial aspects that are associated with chronic low back pain. Pain education is the umbrella term utilized to encompass any type of education to the patient about their chronic pain. Therapeutic exercise in combination with pain education may allow for more well-rounded and effective treatment for patients with chronic nonspecific low back pain (NS-LBP). Clinical Question: Does pain education combined with therapeutic exercise, compared with therapeutic exercise alone, improve patient pain in adults with chronic NS-LBP over a 2- to 3-month treatment period? Summary of Key Findings: A thorough literature review yielded 8 studies potentially relevant to the clinical question, and 3 studies that met the inclusion criteria were included. The 3 studies included reports that exercise therapy reduced symptoms. Two of the 3 included studies support the claim that exercise therapy reduces the symptoms of chronic NS-LBP when combined with pain education, whereas one study found no difference between pain education with therapeutic exercise. Clinical Bottom Line: There is moderate evidence to support the use of pain education along with therapeutic exercise when attempting to reduce symptoms of pain and disability in patients with chronic NS-LBP. Educational interventions should be created to educate patients about the foundation of pain, and pain education should be implemented as a part of the clinician's strategy for the rehabilitation of patients with chronic NS-LBP. Strength of Recommendation: Grade B evidence exists to support the use of patient education with therapeutic exercise for decreasing pain in patients with chronic NS-LBP.

Improvements in Lower-Extremity Function Following a Rehabilitation Program With Patterned Electrical Neuromuscular Stimulation in Females With Patellofemoral Pain: A Randomized Controlled Trial.

CONTEXT: Patellofemoral pain (PFP) is a challenging condition, with altered kinematics and muscle activity as 2 common impairments. Single applications of patterned electrical neuromuscular stimulation (PENS) have improved both kinematics and muscle activity in females with PFP; however, the use of PENS in conjunction with a rehabilitation program has not been evaluated. OBJECTIVE: To determine the effects of a 4-week rehabilitation program with PENS on lower-extremity biomechanics and electromyography (EMG) during a single-leg squat (SLS) and a step-down task (SDT) in individuals with PFP. STUDY DESIGN: Double-blinded randomized controlled trial. SETTING: Laboratory. Patients of Other Participants: Sixteen females with PFP (age 23.3 [4.9] y, mass 66.3 [13.5] kg, height 166.1 [5.9] cm). INTERVENTION: Patients completed a 4-week supervised rehabilitation program with or without PENS. MAIN OUTCOME MEASURES: Curve analyses for lower-extremity kinematics and EMG activity (gluteus maximus, gluteus medius, vastus medialis oblique, vastus lateralis, biceps femoris, and adductor longus) were constructed by plotting group means and 90% confidence intervals throughout 100% of each task, before and after the rehabilitation program. Mean differences (MDs) and SDs were calculated where statistical differences were identified. RESULTS: No differences at baseline in lower-extremity kinematics or EMG were found between groups. Following rehabilitation, the PENS group had significant reduction in hip adduction between 29% and 47% of the SLS (MD = 4.62° [3.85°]) and between 43% and 69% of the SDT (MD = 6.55° [0.77°]). Throughout the entire SDT, there was a decrease in trunk flexion in the PENS group (MD = 10.91° [1.73°]). A significant decrease in gluteus medius activity was seen during both the SLS (MD = 2.77 [3.58]) and SDT (MD = 4.36 [5.38]), and gluteus maximus during the SLS (MD = 1.49 [1.46]). No differences were seen in the Sham group lower-extremity kinematics for either task. CONCLUSION: Rehabilitation with PENS improved kinematics in both tasks and decreased EMG activity. This suggests that rehabilitation with PENS may improve muscle function during functional tasks.

An Innovative Network Approach to Coordinating a National Effort to Improve Cardiovascular Health: The Case of Million Hearts.

OBJECTIVE: To assess the structure, content, quality, and quantity of partnerships that developed in response to a national cardiovascular health initiative, Million Hearts. DESIGN: This study used a social network analysis (SNA) approach to assess the Million Hearts initiative network partnerships and identify potential implications for policy and practice. SETTING/PARTICIPANTS: The Million Hearts network comprised a core group of federal and private sector partners that participate in Million Hearts activities and align with initiative priorities. To bound the network for the SNA, we used a list of 58 organizations (74% response rate) from a previously completed qualitative analysis of Million Hearts partnerships. MAIN OUTCOME MEASURES: We used the online PARTNER (Program to Analyze Record and Track Networks to Enhance Relationships-www.partnertool.net) survey to collect data on individual organizational characteristics and relational questions that asked organizations to identify and describe their relationships with other partners in the network. Key SNA measures include network density, centralizations, value, and trust. RESULTS: Our analyses show a network that is decentralized, has strong perceptions of trust and value among its members, and strong agreement on intended outcomes. Interestingly, partners report a desire and ability to contribute resources to Million Hearts; however, the perceptions between partners are that resources are not being contributed at the level they potentially could be. The majority of partners reported that being in the network helped them achieve their goals related to cardiovascular disease prevention. The largest barrier to successful activities within the network was cited as lack of targeted funding and staff to support participation in the network. CONCLUSIONS: The Million Hearts network described in this article is unique in its membership at the national level, agreement on outcomes, its powerful information-sharing abilities that require few resources, and its decentralized structure. We identified strategies that could be implemented to strengthen the network and its activities. By examining a national-level public-private partnership formed to address a public health issue, we can identify ways to strengthen the network and provide a framework for developing other initiatives.

Open Water Swimming: Medical and Water Quality Considerations.

The sport of open water swimming (OWS) has been popularized on a global scale. This population of athletes may experience several unique medical conditions, necessitating a review of medical issues and environmental considerations. Clinicians providing care for OWS athletes should be educated and trained to recognize and manage illnesses and conditions that often occur in an effort to ensure athlete safety. This article focuses on the major medical challenges faced in OWS, including a review of cardiorespiratory conditions and infections, competitor factors, water quality concerns, and risk minimization strategies.

Targeted Ligand-Exchange Chemistry on Cesium Lead Halide Perovskite Quantum Dots for High-Efficiency Photovoltaics.

The ability to manipulate quantum dot (QD) surfaces is foundational to their technological deployment. Surface manipulation of metal halide perovskite (MHP) QDs has proven particularly challenging in comparison to that of more established inorganic materials due to dynamic surface species and low material formation energy; most conventional methods of chemical manipulation targeted at the MHP QD surface will result in transformation or dissolution of the MHP crystal. In previous work, we have demonstrated record-efficiency QD solar cells (QDSCs) based on ligand-exchange procedures that electronically couple MHP QDs yet maintain their nanocrystalline size, which stabilizes the corner-sharing structure of the constituent PbI64- octahedra with optoelectronic properties optimal for solar energy conversion. In this work, we employ a variety of spectroscopic techniques to develop a molecular-level understanding of the MHP QD surface chemistry in this system. We individually target both the anionic (oleate) and cationic (oleylammonium) ligands. We find that atmospheric moisture aids the process by hydrolysis of methyl acetate to generate acetic acid and methanol. Acetic acid then replaces native oleate ligands to yield QD surface-bound acetate and free oleic acid. The native oleylammonium ligands remain throughout this film deposition process and are exchanged during a final treatment step employing smaller cations-namely, formamidinium. This final treatment has a narrow processing window; initial treatment at this stage leads to a more strongly coupled QD regime followed by transformation into a bulk MHP film after longer treatment. These insights provide chemical understanding to the deposition of high-quality, electronically coupled MHP QD films that maintain both quantum confinement and their crystalline phase and attain high photovoltaic performance.

Evaluating Art Therapy to Heal the Effects of Trauma Among Refugee Youth: The Burma Art Therapy Program Evaluation.

BACKGROUND: Art therapy uses the creative process to encourage personal growth and alleviate symptoms of mental illness. The Art Therapy Institute provides programs for refugee adolescents from Burma to decrease their trauma-related symptoms. This article describes and discusses the methods and findings from an evaluation of this program. The challenges of assessing art therapy with this population and assessment tool gaps are explored and suggestions for future evaluations discussed. METHOD: Four validated clinical assessment tools were administered to 30 participants at baseline and follow-up to measure symptoms of anxiety, depression, and behavioral problems. Focus group discussions with clinicians were used to assess the evaluation. RESULTS: Nearly all participants had experienced one or more traumatic events. At baseline, results showed a higher prevalence of depression than national rates among adolescents. Follow-up results showed improvements in anxiety and self-concept. Qualitative findings suggest that specific benefits of art therapy were not adequately captured with the tools used. DISCUSSION: This evaluation showed some effects of art therapy; however, symptom-focused assessment tools are not adequate to capture clients' growth resulting from the traumatic experience and this unique intervention. Future evaluations will benefit by using an art-based assessment and measuring posttraumatic growth.

Patient-Reported Outcomes at Return to Sport After Lateral Ankle Sprain Injuries: A Report From the Athletic Training Practice-Based Research Network.

CONTEXT: Limited evidence exists regarding the assessment of single-item patient-reported outcomes when patients are medically cleared to return to sport after a lateral ankle sprain (LAS) injury. OBJECTIVE: To evaluate self-reports of improvement in health status, pain, function, and disability at return to sport after an LAS. DESIGN: Descriptive study. SETTING: Sixty-nine athletic training facilities across 24 states. PATIENTS OR OTHER PARTICIPANTS: A total of 637 patients (males = 53.2%) who were diagnosed with an LAS, restricted from sport after injury, and subsequently medically cleared to return to sport within 60 days were included. MAIN OUTCOME MEASURE(S): Descriptive statistics were used to summarize scores for health status (Global Rating of Change), pain (Numeric Pain Rating Scale), function (Global Rating of Function), and disability (Global Rating of Disability). Mann-Whitney U tests were used to compare score differences between sexes. A Kaplan-Meier analysis was performed to provide a visual depiction of sex differences in the time to return to sport. RESULTS: Most patients sustained an LAS injury while participating in basketball, football, or soccer and were cleared to return to sport 8 days after injury. More than two-thirds of patients reported a meaningful improvement in health status between the time of injury and return to sport. However, many noted deficits related to pain (65.1%), function (86.2%), or disability (35.8%) at return to sport. No differences were seen between males and females for pain (P = .90), function (P = .68), change in health status (P = .45), or disability (P = .21) at return to sport, although males returned to sport slightly sooner than females (P = .025). CONCLUSIONS: Despite self-perceived improvements in health status since the time of injury, patients typically returned to sport with deficits in pain, function, and disability after an LAS. Patients may be returning to unrestricted sport participation before they feel their bodies have fully recovered from the injury.

Injury and Treatment Characteristics of Middle School-Aged Patients Under the Care of Athletic Trainers from 2010-2022: A Report from the Athletic Training Practice-Based Research Network.

CONTEXT: Exploring sports-related musculoskeletal injuries and treatment characteristics in middle school sports may help inform patient care decisions such as appropriate medical coverage. OBJECTIVE: To describe injury and treatment characteristics of middle school-aged athletes receiving care from athletic trainers within the Athletic Training Practice-Based Research Network (AT-PBRN). DESIGN: Descriptive study. SETTING: Middle school. PATIENT OR OTHER PARTICIPANTS: Middle school-aged athletes (n=1,011; male=503, female=506) with sports-related musculoskeletal injuries. MAIN OUTCOME MEASURE(S): Electronic patient records were analyzed from the AT-PBRN from 59 athletic trainers across 14 states between 2010-2022. Summary statistics (frequency, percentages, median, interquartile ranges [IQR]) were used to describe injury (age at injury, sex, sport, body part, diagnosis) and treatment characteristics (type of treatment, number of visits, number of procedures per visit). RESULTS: Football (17.7%, n=179), basketball (17.6%, n=178), and soccer (14.9%, n=151) reported the highest number of injuries. Ankle (17.2%, n=174), knee (16.5%, n=167), and head (14.1%, n=143) were the most common injury locations. Concussion (13.0%, n=131), ankle strain/sprain (12.4%, n=125), and thigh/hip/groin sprain/strain (11.1%, n=112) were the most reported diagnoses. Therapeutic exercise or activities (25.6%, n=1068), athletic trainer evaluation or re-evaluation (22.9%, n=957) and hot/cold packs (18.4%, n=766) were the most common services with a median of 2 visits (IQR=1-4) and 2 procedures (IQR=1-2) per visit. CONCLUSIONS: Football, basketball, and soccer reported the most musculoskeletal injuries for middle school-aged athletes. Concussions were the most frequent diagnosis, followed by ankle sprains/strains. Our findings are similar to prior investigations at high school and collegiate levels. Treatments at the middle school level were also similar to those that have been previously reported at the high school level with therapeutic exercise/activity, athletic trainer evaluation or re-evaluation, and hot/cold packs being the most common treatments. This information may be useful for informing patient care decisions at the middle-school level.

The Clinical Laboratory Is an Integral Component to Health Care Delivery : An Expanded Representation of the Total Testing Process.

OBJECTIVES: Developing an expanded representation of the total testing process that includes contemporary elements of laboratory practice can be useful to understanding and optimizing testing workflows across clinical laboratory and patient care settings. METHODS: Published literature and meeting reports were used by the coauthors to inform the development of the expanded representation of the total testing process and relevant examples describing its uses. RESULTS: A visual representation of the total testing process was developed and contextualized to patient care scenarios using a number of examples covering the detection of blood culture contamination, use of next-generation sequencing, and pharmacogenetic testing. CONCLUSIONS: The expanded representation of the total testing process can serve as a model and framework to document and improve the use of clinical testing within the broader context of health care delivery. This representation recognizes increased engagement among clinical laboratory professionals with patients and other health care providers as essential to making informed decisions. The increasing use of data is highlighted as important to ensuring quality, appropriate test utilization, and sustaining an efficient workflow across clinical laboratory and patient care settings. Maintaining a properly resourced and competent workforce is also featured as an essential component to the testing process.

Stability of Mixed Lead Halide Perovskite Films Encapsulated in Cyclic Olefin Copolymer at Room and Cryogenic Temperatures.

Lead Mixed Halide Perovskites (LMHPs), CsPbBrI2, have attracted significant interest as promising candidates for wide bandgap absorber layers in tandem solar cells due to their relative stability and red-light emission with a bandgap ∼1.7 eV. However, these materials segregate into Br-rich and I-rich domains upon continuous illumination, affecting their optical properties and compromising the operational stability of devices. Herein, we track the microscopic processes occurring during halide segregation by using combined spectroscopic measurements at room and cryogenic temperatures. We also evaluate a passivation strategy to mitigate the halide migration of Br/I ions in the films by overcoating with cyclic olefin copolymer (COC). Our results explain the correlation between grain size, intensity dependencies, phase segregation, activation energy barrier, and their influence on photoinduced carrier lifetimes. Importantly, COC treatment increases the lifetime charge carriers in mixed halide thin films, improving efficient charge transport in perovskite solar cell applications.

Multiomic analysis of homologous recombination-deficient end-stage high-grade serous ovarian cancer.

High-grade serous ovarian cancer (HGSC) is frequently characterized by homologous recombination (HR) DNA repair deficiency and, while most such tumors are sensitive to initial treatment, acquired resistance is common. We undertook a multiomics approach to interrogate molecular diversity in end-stage disease, using multiple autopsy samples collected from 15 women with HR-deficient HGSC. Patients had polyclonal disease, and several resistance mechanisms were identified within most patients, including reversion mutations and HR restoration by other means. We also observed frequent whole-genome duplication and global changes in immune composition with evidence of immune escape. This analysis highlights diverse evolutionary changes within HGSC that evade therapy and ultimately overwhelm individual patients.

High School Athletes' Health-Related Quality of Life Across Recovery After Sport-Related Concussion or Acute Ankle Injury: A Report From the Athletic Training Practice-Based Research Network.

BACKGROUND: Evaluating adolescent athletes' perceived health status after a sport-related injury can provide important direction for health promotion strategies and preparation for a successful return to play. Furthermore, comparing specific injury types regarding their impact on athletes' perspectives of their global and domain-specific health perceptions allows for a more detailed understanding of an athlete's experience while also providing avenues for targeted treatment strategies. PURPOSE: To compare health-related quality of life (HRQOL) between high school athletes who had sustained either a concussion or an acute ankle injury and compare how these injury types related to their global and domain-specific HRQOL across recovery. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Electronic medical records created by athletic trainers working in 32 high school facilities were examined, and records from 1749 patients who sustained either a sport-related concussion (n = 862) or ankle sprain (n = 887) were screened for inclusion. HRQOL was assessed by self-reported scores on the Pediatric Quality of Life Inventory (PedsQL) at 2 time points after injury (T1 = 0-2 days; T2 = 11-29 days). A 2-way group by time analysis of variance was conducted to examine differences in trajectories and disrupted areas of HRQOL. RESULTS: Overall, 85 patient cases (46 concussion, 39 ankle sprain) fit the inclusion criteria. Each injury group exhibited improved global and domain-specific PedsQL scores between their 2 measured time points (P < .05), indicating recovery. However, domain-specific comparisons revealed that at T2, patients who had sustained an ankle sprain reported significantly lower PedsQL physical functioning scores (78.3 ± 19.3 vs 86.2 ± 15.7 for concussion; P = .005), whereas patients who had sustained a concussion reported lower scores related to their school functioning (80.0 ± 20.0 vs 90.8 ± 12.7 for ankle sprain; P = .006). CONCLUSION: The study results indicated that in high school athletes, the trajectories and disrupted areas of HRQOL stemming from a sport-related injury may be influenced differentially when comparing concussions with ankle sprains.

Patient-Reported Outcome Measures for Pediatric Patients With Sport-Related Injuries: A Systematic Review.

Despite a call to incorporate patient-reported outcome measures (PROMs) into all aspects of health care, little is known about which instruments are best suited for a pediatric patient population with sport-related injury. The objective of this article was to perform a systematic review of the currently available evidence to determine which PROMs were used for pediatric patients with sport-related injuries and identify the associated psychometric properties and considerations for clinical utility. We conducted a literature search for articles on PROMs used in the pediatric population through electronic databases and a manual search of reference lists and authors between from inception to 2020. Articles were grouped based on the PROM(s) included, and considerations for clinical utility and psychometric properties were extracted from each article. Thirty-nine articles were included in this review, from which 22 PROMs were identified: 12 PROMs were developed specifically for the pediatric population, 4 were modified versions of an adult scale, and 6 were adult measures used in a pediatric population. Of the PROMs included in this review, the Oxford Ankle Foot Questionnaire for Children and the Pediatric Quality of Life Inventory were the most comprehensive in their development and assessment. Several outcome measures used for pediatric patients had missing or inadequate measurement properties and considerations for clinical utility, particularly in regard to readability, responsiveness, and interpretability. Clinicians and researchers should consider a measure's feasibility, acceptability, appropriateness, and psychometric properties when selecting a PROM for use with the pediatric population.