Telemedicine Follow-up After Medication Management of Early Pregnancy Loss.

Objective: Our objective was to evaluate the feasibility of a new protocol for telemedicine follow-up after medication management of early pregnancy loss. Study Design: The study was designed to assess the feasibility of planned telemedicine follow-up after medication management of early pregnancy loss. We compared these follow-up rates with those after planned in-person follow-up of medication management of early pregnancy loss and planned telemedicine follow-up after medication abortion. We conducted a retrospective cohort study, including patients initiating medication management of early pregnancy loss <13w0d gestation and medication abortion ≤10w0d with a combination of mifepristone and misoprostol between April 1, 2020, and March 28, 2021. As part of a new clinical protocol, patients could opt for telemedicine follow-up one week after treatment and a home urine pregnancy test 4 weeks after treatment. Our primary outcome was completed follow-up as per clinical protocol. We also examined outcomes related to complications across telemedicine and in-person follow-up groups. Results: Of patients reviewed, 181 were eligible for inclusion; 75 had medication management of early pregnancy loss, and 106 had medication abortion. Thirty-six out of 75 patients elected for telemedicine follow-up after early pregnancy loss. Of patients scheduled for telemedicine follow-up, 29/36 (81%, 95% CI: 64-92) with early pregnancy loss and 64/69 (93%, 95% CI: 84-98) undergoing medication abortion completed follow-up as per protocol (p = 0.06). Completed follow-up was also similar among patients undergoing medication management of early pregnancy loss who planned for in-person follow-up (p = 0.135). Complications were rare and did not differ across early pregnancy loss and medication abortion groups. Conclusions: Telemedicine follow-up is a feasible alternative to in-person assessment after medication management of early pregnancy loss.

Improving Health and Reducing Chronic Disease Disparities with Latinx Communities: Evaluating the Role of Documented Community-Based Intervention Participation.

PURPOSE: Limited evidence exists on the impact of participation in community-based chronic disease self-management and prevention programs on health disparities. The purpose of this research was to determine the effects of participation in the Healthy Here Wellness Referral System on existing disparities in glycated hemoglobin (HbA1c), systolic blood pressure (BP), and diastolic BP among Hispanic/Latinx adults compared with non-Hispanic White adults. METHODS: We merged administrative clinical and referral data from 2018 through 2022 for adult patients in six focus ZIP codes in New Mexico resulting in a sample of 1331 patients and used regression models to examine predictors of intervention participation as well as propensity-adjusted impacts of participation on HbA1c and BP outcomes. RESULTS: Non-Hispanic White patients who were referred to community-based programming but did not participate saw statistically significant increases in HbA1c. Hispanic/Latinx patients saw statistically significant decreases in HbA1c with referral alone, with no added benefit from program participation. The impact of participation differed statistically significantly (t(683) = 3.55, p < .001) between these two groups for HbA1c levels, as well as for systolic (t(958) = 2.11, p = .04) and diastolic BP outcomes (t(958) = 2.96, p = .003). CONCLUSIONS: Results of this study support the promise of using centralized referral systems to co-produce health improvement in community settings. Mixed findings highlight the need for further uptake of theory-informed measurement in evaluations seeking to understand heterogeneous program impacts by race and ethnicity.

Decorin and/or biglycan knockdown in aged mouse patellar tendon impacts fibril morphology, scar area, and mechanical properties.

Small leucine-rich proteoglycans, such as decorin and biglycan, play pivotal roles in collagen fibrillogenesis during development, healing, and aging in tendon. Previous work has shown that the absence of decorin and biglycan affects fibril shape and mechanical properties during tendon healing. However, the roles of decorin and biglycan in the healing process of aged tendons are unclear. Therefore the objective of this study was to evaluate the differential roles of decorin and biglycan during healing of patellar tendon injury in aged mice. Aged (300 days old) female Dcn+/+/Bgn+/+ control (WT, n = 52), Dcnflox/flox (I-Dcn-/-, n = 36), Bgnflox/flox (I-Bgn-/-, n = 36), and compound Dcnflox/flox/Bgnflox/flox (I-Dcn-/-/Bgn-/-, n = 36) mice with a tamoxifen-inducible Cre were utilized. Targeted gene expression, collagen fibril diameter distributions, mechanical properties, and histological assays were employed to assess the effects of knockdown of decorin and/or biglycan at the time of injury. Knockdown resulted in alterations in fibril diameter distribution and scar area, but surprisingly did not lead to many differences in mechanical properties. Biglycan played a larger role in early healing stages, while decorin is more significant in later stages, particularly in scar remodeling. This study highlights some of the differential roles of biglycan and decorin in the regulation of fibril structure and scar area, as well as influencing gene expression during healing in aged mice.

Novice users' brain activity and biomechanics change after practicing walking with an ankle exoskeleton.

Walking with an exoskeleton represents a sophisticated interplay between human physiology and mechanical augmentation, yet understanding of cortical responses in this context remains limited. To address this gap, this study aimed to explore cortical responses during walking with an ankle exoskeleton, examining how these responses evolve with familiarity to the augmentation. Healthy participants without prior exoskeleton experience underwent EEG, EMG, and motion capture analysis while walking with exoskeleton assistance at 1.2m/s. Initially, exoskeleton-assisted walking induced significant biomechanical changes accompanied by corresponding cortical alterations, leading to increased cortical involvement. In addition, after a brief familiarization period, significant increases in alpha band cortical power were observed, indicating decreased cortical engagement. These findings hold significance for elucidating the cortical mechanisms involved in exoskeleton-assisted walking and may contribute to the development of more seamlessly integrated augmentation devices.

Gender Communication Differences on a Pediatric Provider Listserv.

BACKGROUND AND OBJECTIVES: Gender-based communication differences are described in educational online communities, but have not been rigorously evaluated in medical online communities. Understanding gender differences in communication may provide insight into gender disparities in the medical profession. Our objective was to describe gender differences in post frequency, content, and language styles on the American Academy of Pediatrics Section on Hospital Medicine (SOHM) listserv. METHODS: Posts were obtained from publicly available SOHM listserv archives. The first month of every quarter of 2019 and 2020 were reviewed. Two reviewers assigned a post topic (clinical, research, etc) and format (question vs statement) to all deidentified original posts (K = 1.0 topic, 0.89 format). Six trained reviewers assigned language styles (intraclass coefficient = 0.73, indicating good agreement). RESULTS: We analyzed 1592 posts: 287 original posts and 1305 responses. Frequency: Women authored 50% of posts. The 9 most frequent posters (7 men, 2 women) accounted for 19.5% of posts. Content: Men's posts had more words than women's (132.51 vs 112.3, P ≤ .01). Men were more likely to post about health policy and research (P < .001). Men were more likely to post statements compared with women (39% vs 21%, P < .001). Style: Men's posts were more likely to be coded adversarial (12.3% vs 5.5%, P < .001) authoritative (12.2% vs 6.5%, P < .001) or self-amplifying (6.5% vs 3.6%, P < .001). CONCLUSIONS: Women contribute disproportionately fewer posts to the American Academy of Pediatrics SOHM listserv compared with their percentage in the subspecialty. We noted significant gender differences in language style and content, which may impact career development and online community inclusion.

A theory-driven organ donation campaign: a field intervention among university students in Iran.

Background: This study conducted an empirical evaluation of an intervention derived from the theory of planned behavior (TPB) aimed at implementing a health campaign among medical students at Shahid Beheshti University of Medical Sciences. Methods: In this interventional study, a valid and reliable TPB-based questionnaire was administered before launching a health campaign titled "Organ Donation=Life Donation" among 260 medical students. The campaign was structured around nine steps: situation analysis, goal identification, target audience identification, strategy development, tactics establishment, media selection, timetable creation, budget planning, and program evaluation. Two months after the campaign, participants completed a posttest and were offered an organ donation card. Data analysis was conducted using SPSS ver. 16, employing descriptive statistics (frequency and percentage) and tests such as the Kolmogorov-Smirnov test and the paired-samples t-test. Results: All participants adopted more prodonation stances across all constructs measured, both immediately and 2 months after exposure to the health campaign, compared to their pretest scores. These results indicate that the health campaign had a significant impact on psychological variables such as attitudes (P<0.001), subjective norms (P<0.001), and perceived behavioral control (P<0.038), as well as on the actual acceptance of an organ donor card. Conclusions: Effective health education and promotion interventions, including health campaigns, are essential to encourage the use of organ donation cards. Additionally, current experiences indicate that the TPB serves as a suitable theoretical framework for designing organ donation interventions.

Evaluating Mental Health First Aid for Illinois Agricultural Communities.

Introduction. Mental Health First Aid (MHFA) was created to teach individuals how to identify, understand, and respond to signs of mental illnesses and substance use disorders. Programs like this may be essential for agricultural communities where suicide rates have increased, and mental health stigma has been a barrier to this population. This study evaluated how effective MHFA and Youth MHFA were for participants from agricultural communities. Methods. Participants completed the MHFA (N = 38) and Youth MHFA (N = 66) programs in 2021-2022, and Extension educators offered both programs as a part of outreach efforts within agricultural contexts. Participants completed pre-, post-, and post-only evaluations as standardized by the National Council for Mental Wellbeing. Results. After completing the MHFA and Youth MHFA training, participants increased their knowledge, confidence, and skills in various mental health topics. This includes early indicators of mental health challenges, the ability to have supportive conversations, and how to provide resources to others. For example, most participants felt they became more knowledgeable about MHFA (69%) and the ability to recognize the signs and symptoms of mental health or substance use challenges (65%). Conclusion. This research has implications for supporting agricultural workers through additional mental health training, managing farm stress, and understanding mental health stigma within this community.

Ethical futures in biological anthropology: Research, teaching, community engagement, and curation involving deceased individuals.

Although ethical reforms in biological anthropology have gained ground in recent years, there is still a scarcity of ethical standards for work involving historical documented collections (HDCs) at US museums and universities. These collections of deceased individuals were created in the late 19th to mid-20th centuries under anatomy laws that targeted socially marginalized communities and allowed for the dissection of these individuals without their consent. Due to the extensive information associated with the individuals and made available to researchers, these collections have served as foundational resources for theory and methods development in biological anthropology into the 21st century. Recognizing the need for ethical guidelines for research, teaching and training, community engagement, and curation involving HDCs, we held a workshop called "Ethical Futures for Curation, Research, and Teaching in Biological Anthropology" on November 15-17, 2021. Here we summarize the conversations and major points of consensus among the workshop participants on these topics in order to advance these ethical considerations more broadly across the field.

Combining EHMT and PARP Inhibition: A Strategy to Diminish Therapy-Resistant Ovarian Cancer Tumor Growth while Stimulating Immune Activation.

Despite the success of poly-ADP-ribose polymerase inhibitors (PARPi) in the clinic, high rates of resistance to PARPi presents a challenge in the treatment of ovarian cancer, thus it is imperative to find therapeutic strategies to combat PARPi resistance. Here, we demonstrate that inhibition of epigenetic modifiers euchromatic histone lysine methyltransferases 1/2 (EHMT1/2) reduces the growth of multiple PARPi-resistant ovarian cancer cell lines and tumor growth in a PARPi-resistant mouse model of ovarian cancer. We found that combinatory EHMT and PARP inhibition increases immunostimulatory double-stranded RNA formation and elicits several immune signaling pathways in vitro. Using epigenomic profiling and transcriptomics, we found that EHMT2 is bound to transposable elements, and that EHMT inhibition leads to genome-wide epigenetic and transcriptional derepression of transposable elements. We validated EHMT-mediated activation of immune signaling and upregulation of transposable element transcripts in patient-derived, therapy-naïve, primary ovarian tumors, suggesting potential efficacy in PARPi-sensitive disease as well. Importantly, using multispectral immunohistochemistry, we discovered that combinatory therapy increased CD8 T-cell activity in the tumor microenvironment of the same patient-derived tissues. In a PARPi-resistant syngeneic murine model, EHMT and PARP inhibition combination inhibited tumor progression and increased Granzyme B+ cells in the tumor. Together, our results provide evidence that combinatory EHMT and PARP inhibition stimulates a cell autologous immune response in vitro, is an effective therapy to reduce PARPi-resistant ovarian tumor growth in vivo, and promotes antitumor immunity activity in the tumor microenvironment of patient-derived ex vivo tissues of ovarian cancer.

Interpersonal discrimination and depressive symptoms among older Black and African American adults.

To examine the association between recent experiences of discrimination and depressive symptom presentation and severity among a U.S. sample of older Black and African American adults. A cross-sectional survey of 124 Black and African American adults aged 50 and older in the United States was conducted assessing interpersonal discrimination and depressive symptoms. The Perceived Ethnic Discrimination Questionnaire assessed four forms of interpersonal discrimination. A measure of heightened vigilance to bias assessed anticipatory coping with discrimination experiences. Past-month affective and somatic symptoms of depression were assessed using the Depressive and Somatic Symptoms Scale. All forms of interpersonal racial discrimination were positively associated with greater affective symptom severity. Being avoided, devalued, and threatened or actively physically harmed were associated with greater somatic symptom severity. Vigilant coping was positively associated with affective symptom severity but not somatic symptom severity. Racial discrimination is linked to depression severity among older Black and African American and varies by symptom. This study helps inform work on processes linking discrimination with poorer psychological outcomes and will allow for more effective interventions and prevention efforts that are tailored to older minority populations.

The role of competency based medical education in addressing health inequities and cultivating inclusive learning environments.

Pediatric health inequities are pervasive and reflect the confluence of social and structural determinants of health including racism in all its forms. Current approaches in graduate medical education that prepare trainees to address health inequities and improve population health are inadequate. Competency based medical education (CBME) can advance equity-oriented efforts to improve patient outcomes, optimize the learning environment and encourage lifelong learning. We briefly describe the impact of racism and discrimination on the clinical learning environment. We then highlight how to apply the 5 core principles of CBME to equip learners across the continuum to address health inequities. We provide specific examples including 1) how CBME can inform teaching, assessment and professional development activities to promote equitable pediatric health outcomes via enturstable professional activities, 2) competency-focused instruction that address racism and inequities, 3) multimodal learning approaches to facilitate the acquisition of the desired competencies to address health inequities, 4) sequenced learning approaches across the continuum of practicing pediatricians, and 5) tools and resources for programmatic assessment of trainee and program performance in addressing pediatric health inequities.

Misaligned Supports: Differences in Reported Health Care Worker Well-being Supports Provided and Needed During the COVID-19 Pandemic.

PURPOSE: To describe the well-being supports provided to health care workers (HCWs) during the COVID-19 pandemic in health centers and hospitals. DESIGN: Cross-sectional qualitative interviews before and after implementation of a peer-based support intervention. SETTING: Purposively sampled hospitals and health centers across the US. PARTICIPANTS: 28 site leaders and 56 HCWs sampled from 16 hospitals and 12 health centers. METHOD: Site leaders and HCWs were asked to describe supports available to HCWs during the COVID-19 pandemic. Thematic and content coding and analysis of interview responses were conducted using Dedoose. RESULTS: Both site leaders and HCWs identified a range of support resources available. Communication resources were the most frequently cited in both groups. Health care workers reported bi-directional communication, while one-way communication was emphasized by site leaders. Hospitals highlighted counseling support, particularly Employee Assistance Programs (EAP), while health centers prioritized community support. Wellness activities were more prevalent in hospital settings, while health centers offered specific workplace-provided training for HCWs. Health care workers encountered barriers when accessing support, including limited time, fear of stigma, and disruptions to their existing support networks attributable to the pandemic. CONCLUSION: While there are resources for HCWs, the available supports may not align with their needs and barriers to access may limit the effectiveness of these supports. Continued engagement between leaders and HCWs could help better align resources with needs.

MAPK13 controls structural remodeling and disease after epithelial injury.

All living organisms are charged with repair after injury particularly at epithelial barrier sites, but in some cases this response leads instead to structural remodeling and long-term disease. Identifying the molecular and cellular control of this divergence is key to disease modification. In that regard, stress kinase control of epithelial stem cells is a rational entry point for study. Here we examine the potential for mitogen-activated protein kinase 13 (MAPK13) regulation of epithelial stem cells using models of respiratory viral injury and post-viral lung disease. We show that Mapk13 gene-knockout mice handle acute infectious illness as expected but are protected against structural remodeling manifest as basal-epithelial stem cell (basal-ESC) hyperplasia-metaplasia, immune activation, and mucinous differentiation. In corresponding cell models, Mapk13-deficiency directly attenuates basal-ESC growth and organoid formation. Extension to human studies shows marked induction/activation of basal-cell MAPK13 in clinical samples of comparable remodeling found in asthma and COPD. Here again, MAPK13 gene-knockdown inhibits human basal-ESC growth in culture. Together, the data identify MAPK13 as a control for structural remodeling and disease after epithelial injury and as a suitable target for down-regulation as a disease-modifying strategy.

Profiling phagosome proteins identifies PD-L1 as a fungal-binding receptor.

Phagocytosis is the process by which myeloid phagocytes bind to and internalize potentially dangerous microorganisms1. During phagocytosis, innate immune receptors and associated signalling proteins are localized to the maturing phagosome compartment, forming an immune information processing hub brimming with microorganism-sensing features2-8. Here we developed proximity labelling of phagosomal contents (PhagoPL) to identify proteins localizing to phagosomes containing model yeast and bacteria. By comparing the protein composition of phagosomes containing evolutionarily and biochemically distinct microorganisms, we unexpectedly identified programmed death-ligand 1 (PD-L1) as a protein that specifically enriches in phagosomes containing yeast. We found that PD-L1 directly binds to yeast upon processing in phagosomes. By surface display library screening, we identified the ribosomal protein Rpl20b as a fungal protein ligand for PD-L1. Using an auxin-inducible depletion system, we found that detection of Rpl20b by macrophages cross-regulates production of distinct cytokines including interleukin-10 (IL-10) induced by the activation of other innate immune receptors. Thus, this study establishes PhagoPL as a useful approach to quantifying the collection of proteins enriched in phagosomes during host-microorganism interactions, exemplified by identifying PD-L1 as a receptor that binds to fungi.

Metagenomic and paleopathological analyses of a historic documented collection explore ancient dental calculus as a diagnostic tool.

Dental calculus is a microbial biofilm that contains biomolecules from oral commensals and pathogens, including those potentially related to cause of death (CoD). To assess the utility of calculus as a diagnostically informative substrate, in conjunction with paleopathological analysis, calculus samples from 39 individuals in the Smithsonian Institution's Robert J. Terry Collection with CoDs of either syphilis or tuberculosis were assessed via shotgun metagenomic sequencing for the presence of Treponema pallidum subsp. pallidum and Mycobacterium tuberculosis complex (MTBC) DNA. Paleopathological analysis revealed that frequencies of skeletal lesions associated with these diseases were partially inconsistent with diagnostic criteria. Although recovery of T. p. pallidum DNA from individuals with a syphilis CoD was elusive, MTBC DNA was identified in at least one individual with a tuberculosis CoD. The authenticity of MTBC DNA was confirmed using targeted quantitative PCR assays, MTBC genome enrichment, and in silico bioinformatic analyses; however, the lineage of the MTBC strain present could not be determined. Overall, our study highlights the utility of dental calculus for molecular detection of tuberculosis in the archaeological record and underscores the effect of museum preparation techniques and extensive handling on pathogen DNA preservation in skeletal collections.

The vaginal microbiome and HIV transmission dynamics.

PURPOSE OF REVIEW: Among women, having a nonoptimal, highly diverse vaginal microbiome dominated by bacteria other than optimal Lactobacillus species such as L. crispatus or L. jensenii predicts HIV transmission. Reducing HIV acquisition among women requires a better understanding of the mechanisms through which the vaginal microbiome impacts HIV transmission dynamics and how to more effectively treat and intervene. Technological advancements are improving the ability of researchers to fully characterize interacting host-bacteria mechanisms. Consequently, the purpose of this review was to summarize the most innovative research on the vaginal microbiome and its role in HIV transmission in the past year. RECENT FINDINGS: Studies combining multiomics, experimental, and translational approaches highlight the associations of a nonoptimal microbiome with maladaptive alterations in immune cell functioning, vaginal metabolites, host cell transcription, mucosal immunity, and epithelial barrier integrity. While there are multiple mechanisms proposed to increase HIV acquisition risk, there are virtually zero acceptable and effective treatments to improve the vaginal microbiome and immunity. SUMMARY: Women-centered solutions to modify the vaginal microbiome and bacterial metabolites should continue to be explored as a mechanism to reduce HIV acquisition.

Working Memory Recovery in Adolescents with Concussion: Longitudinal fMRI Study.

Background: Understanding the behavioral and neural underpinnings of the post-concussion recovery of working memory function is critically important for improving clinical outcomes and adequately planning return-to-activity decisions. Previous studies provided inconsistent results due to small sample sizes and the use of a mixed population of participants who were at different post-injury time points. We aimed to examine working memory recovery during the first 6 months post-concussion in adolescents. Methods: We used functional magnetic resonance imaging (fMRI) to scan 45 concussed adolescents [CONCs] at baseline (<10 days post-concussion) and at 6 months post-concussion. Healthy control adolescents [HCs; n = 32] without a history of concussion were scanned once. During the scans, participants performed one-back and two-back working memory tasks with letters as the stimuli and angry, happy, neutral, and sad faces as distractors. Results: All affected adolescents were asymptomatic and cleared to return to activity 6 months after concussion. Working memory recovery was associated with faster and more accurate responses at 6 months vs. baseline (p-values < 0.05). It was also characterized by significant difficulty-related activation increases in the left inferior frontal gyrus (LIFG) and the left orbitofrontal cortex (LOFC) at 6 months vs. baseline. Although the activation differences between one-back and two-back were comparable between HCs and CONCs at 6 months, HCs had more pronounced activation in the LIFG than concussed adolescents. Conclusions: Post-concussion recovery is associated with significant performance improvements in speed and accuracy, as well as the normalization of brain responses in the LIFG and LOFC during the n-back task. The observed patterns of LOFC activation might reflect compensatory strategies to distribute neural processing and reduce neural fatigue post-concussion.

Umbilical cord blood-derived therapy for preterm lung injury: a systematic review and meta-analysis.

INTRODUCTION: Lung injuries, such as bronchopulmonary dysplasia (BPD), remain a major complication of preterm birth, with limited therapeutic options. One potential emerging therapy is umbilical cord blood (UCB)-derived therapy. OBJECTIVES: To systematically assess the safety and efficacy of UCB-derived therapy for preterm lung injury in preclinical and clinical studies. METHODS: A systematic search of MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, and WHO International Trials Registry Platform was performed. A meta-analysis was conducted with Review Manager (5.4.1) using a random effects model. Data was expressed as standardized mean difference (SMD) for preclinical data and pooled relative risk (RR) for clinical data, with 95% confidence intervals (CI). Potential effect modifiers were investigated via subgroup analysis. Certainty of evidence was assessed using the GRADE system. RESULTS: Twenty-three preclinical studies and six clinical studies met eligibility criteria. Statistically significant improvements were seen across several preclinical outcomes, including alveolarization (SMD, 1.32, 95%CI [0.99, 1.65]), angiogenesis (SMD, 1.53, 95%CI [0.87, 2.18]), and anti-inflammatory cytokines (SMD, 1.68, 95%CI [1.03, 2.34]). In clinical studies, 103 preterm infants have received UCB-derived therapy for preterm lung injury and no significant difference was observed in the development of BPD (RR, 0.93, 95%CI [0.73, 1.18]). Across both preclinical and clinical studies, administration of UCB-derived therapy appeared safe. Certainty of evidence was assessed as "low." CONCLUSIONS: Administration of UCB-derived therapy was associated with statistically significant improvements across several lung injury markers in preclinical studies. Early clinical studies demonstrated the administration of UCB-derived therapy as safe and feasible but lacked data regarding efficacy.

Combining EHMT and PARP Inhibition: A Strategy to Diminish Therapy-Resistant Ovarian Cancer Tumor Growth while Stimulating Immune Activation.

Despite the success of Poly-ADP-ribose polymerase inhibitors (PARPi) in the clinic, high rates of resistance to PARPi presents a challenge in the treatment of ovarian cancer, thus it is imperative to find therapeutic strategies to combat PARPi resistance. Here, we demonstrate that inhibition of epigenetic modifiers Euchromatic histone lysine methyltransferases 1/2 (EHMT1/2) reduces the growth of multiple PARPi-resistant ovarian cancer cell lines and tumor growth in a PARPi-resistant mouse model of ovarian cancer. We found that combinatory EHMT and PARP inhibition increases immunostimulatory dsRNA formation and elicits several immune signaling pathways in vitro. Using epigenomic profiling and transcriptomics, we found that EHMT2 is bound to transposable elements, and that EHMT inhibition leads to genome-wide epigenetic and transcriptional derepression of transposable elements. We validated EHMT-mediated activation of immune signaling and upregulation of transposable element transcripts in patient-derived, therapy-naïve, primary ovarian tumors, suggesting potential efficacy in PARPi-sensitive disease as well. Importantly, using multispectral immunohistochemistry, we discovered that combinatory therapy increased CD8 T cell activity in the tumor microenvironment of the same patient-derived tissues. In a PARPi-resistant syngeneic murine model, EHMT and PARP inhibition combination inhibited tumor progression and increased Granzyme B+ cells in the tumor. Together, our results provide evidence that combinatory EHMT and PARP inhibition stimulates a cell autologous immune response in vitro, is an effective therapy to reduce PARPi resistant ovarian tumor growth in vivo, and promotes anti-tumor immunity activity in the tumor microenvironment of patient-derived ex vivo tissues of ovarian cancer.

Interpersonal Coordination between Female Soccer Players: Leader-Follower Roles within a Collision-Avoidance Task.

Background/Purpose: Return to sport decision-making may be improved by assessing an athlete's ability to coordinate movement with opponents in sport. The purpose was to investigate whether previous injuries associated with female soccer players' interpersonal coordination during a collision avoidance task. The authors hypothesized that external perturbations would disrupt the strength and stability of coordinated movement, and that individuals with a history of injury would be less likely to recover coordinated movement. Study Design: Cross-Sectional. Methods: Nine female athletes with a history of lower extremity injuries and nine without injuries were paired into dyads. Each dyad completed twenty trials of an externally paced collision-avoidance agility task with an unanticipated perturbation. Participant trajectories were digitized and analyzed using cross-recurrence quantification analysis (CRQA) to determine the strength and stability of interpersonal coordination dynamics. Trials in which participants with injury history assumed leader or follower roles within each dyad were then used to study how dyadic coordination varied across task stages (early, perturbation, and late) using linear mixed effect models. Cohen's d effect sizes were calculated to demonstrate magnitude of differences. In exploratory analysis, psychological readiness (i.e., self-reported knee functioning, fear of injury, and risk-taking propensity) was evaluated for their association with leader-follower status. Results: Perturbation disrupted the strength (R2=0.65, p<0.001, early=49.7±1.7, perturbation=41.1±1.7, d=0.39) and stability (R2=0.71, p < 0.001, early=65.0±1.6, perturbation=58.0±1.7, d=0.38) of interpersonal coordination regardless of leader-follower status. Individuals with injury history failed to restore coordination after the perturbation compared to control participants (injury=44.2.0±2.1, control=50.8±2.6, d=0.39). Neither demographic nor psychological measures were associated with leader-follower roles (B=0.039, p=0.224). Conclusion: Individuals with a history of lower extremity injury may have a diminished ability to adapt interpersonal coordination to perturbations, possibly contributing to a higher risk of re-injury. Level of Evidence: 3.