Learning to lead: The evolution of a pilot leadership curriculum for gynecologic oncology fellows at the Ohio State University.

•Leadership training is under-emphasized in traditional medical education.•An effective leadership curriculum must be dynamic and requires genuine investment from participants.•Through didactic education, self-reflection, and real-world perspective we can actively mold future leaders in gynecologic oncology.

A Provably Convergent Control Closure Scheme for the Method of Moments of the Chemical Master Equation.

In this article, we introduce a novel moment closure scheme based on concepts from model predictive control (MPC) to accurately describe the time evolution of the statistical moments of the solution of the chemical master equation (CME). The method of moments, a set of ordinary differential equations frequently used to calculate the first nm moments, is generally not closed since lower-order moments depend on higher-order moments. To overcome this limitation, we interpret the moment equations as a nonlinear dynamical system, where the first nm moments serve as states, and the closing moments serve as the control input. We demonstrate the efficacy of our approach using three example systems and show that it outperforms existing closure schemes. For polynomial systems, which encompass all mass-action systems, we provide probability bounds for the error between true and estimated moment trajectories. We achieve this by combining the convergence properties of a priori moment estimates from stochastic simulations with guarantees for nonlinear reference tracking MPC. Our proposed method offers an effective solution to accurately predict the time evolution of moments of the CME, which has wide-ranging implications for many fields, including biology, chemistry, and engineering.

Analysis of Ultrasonic Vibration-Assisted Ball Burnishing Process on the Tribological Behavior of AISI 316L Cylindrical Specimens.

In this study, we analyzed the effects of vibration assistance, combined with a ball burnishing process, in terms of topology, residual stresses, and tribological properties on 316L shafts. The burnishing variables consisted of the variation of the input force, the number of passes, and the activation of the vibration assistance, which is based on a 40 kHz frequency and 8 µm of vibration amplitude, derived in a screening design of three factors. The results show that the medium-high level of burnishing force, high level of the number of passes, and the activation of the vibration assistance are the best options in order to improve the average roughness, the microstructure, the increase in the compressive residual stresses, and the wear enhancement, besides all variables being significant in the p-value analysis through ANOVA. Statistically, the vibration-assisted ball burnishing improved the average roughness by 2.9%, enlarged the von Mises stress on the surface by 11.5% and enhanced the wear resistance of a 316L shaft and WC-Co ball contact up to 7.3%.

The impossible challenge of estimating non-existent moments of the Chemical Master Equation.

MOTIVATION: The Chemical Master Equation (CME) is a set of linear differential equations that describes the evolution of the probability distribution on all possible configurations of a (bio-)chemical reaction system. Since the number of configurations and therefore the dimension of the CME rapidly increases with the number of molecules, its applicability is restricted to small systems. A widely applied remedy for this challenge is moment-based approaches which consider the evolution of the first few moments of the distribution as summary statistics for the complete distribution. Here, we investigate the performance of two moment-estimation methods for reaction systems whose equilibrium distributions encounter fat-tailedness and do not possess statistical moments. RESULTS: We show that estimation via stochastic simulation algorithm (SSA) trajectories lose consistency over time and estimated moment values span a wide range of values even for large sample sizes. In comparison, the method of moments returns smooth moment estimates but is not able to indicate the non-existence of the allegedly predicted moments. We furthermore analyze the negative effect of a CME solution's fat-tailedness on SSA run times and explain inherent difficulties. While moment-estimation techniques are a commonly applied tool in the simulation of (bio-)chemical reaction networks, we conclude that they should be used with care, as neither the system definition nor the moment-estimation techniques themselves reliably indicate the potential fat-tailedness of the CME's solution.

Tissue factor as a novel diagnostic target for early detection of ovarian cancer using ultrasound microbubbles.

INTRODUCTION: Ovarian cancer (OC) is the deadliest gynecologic malignancy, with an overall 5-year survival rate of less than 30%. The existing paradigm for OC detection involves a serum marker, CA125, and ultrasound examination, neither of which is sufficiently specific for OC. This study addresses this deficiency through the use of a targeted ultrasound microbubble directed against tissue factor (TF). METHODS: TF expression was examined in both OC cell lines and patient-derived tumor samples via western blotting and IHC. In vivo microbubble ultrasound imaging was analyzed using high grade serous ovarian carcinoma orthotopic mouse models. RESULTS: While TF expression has previously been described on angiogenic, tumor-associated vascular endothelial cells (VECs) of several tumor types, this is first study to show TF expression on both murine and patient-derived ovarian tumor-associated VECs. Biotinylated anti-TF antibody was conjugated to streptavidin-coated microbubbles and in vitro binding assays were performed to assess the binding efficacy of these agents. TF-targeted microbubbles successfully bound to TF-expressing OC cells, as well as an in vitro model of angiogenic endothelium. In vivo, these microbubbles bound to the tumor-associated VECs of a clinically relevant orthotopic OC mouse model. CONCLUSION: Development of a TF-targeted microbubble capable of successfully detecting ovarian tumor neovasculature could have significant implications towards increasing the number of early-stage OC diagnoses. This preclinical study shows potential for translation to clinical use, which could ultimately help increase the number of early OC detections and decrease the mortality associated with this disease.

Recurrence rate in early-stage epithelial ovarian cancer: Is there a role for upfront maintenance with PARP inhibitors in stages I and II?

Objective: To determine the recurrence rate and survival among early-stage epithelial ovarian cancer cases considering homologous recombination deficiency (HRD) status. Methods: Single institution retrospective study of stage I/II EOC patients from 2017 to 2020. HRD was defined as evidence of germline or somatic BRCA mutation, or loss of heterozygosity (LOH)/genomic instability (GIS) as determined by companion diagnostic tests. Kaplan-Meier analyses were performed. Results: 89 stage I/II cases were included. 4/89 (4.5%) had a germline BRCA1/2 mutation, 8 (9%) were germline negative but had a somatic BRCA mutation, and 8 (9%) were BRCA wild-type but had evidence of LOH/GIS on somatic testing; these 20/89 (22%) cases comprised the HRD group. The remaining tumors were confirmed homologous recombination proficient (HRP, 35/89, 39%) or homologous recombination unknown (HRU, 34/89, 38%). The overall recurrence rate was 33/89 (37%). There were more recurrences among HRD cases (14/20, 70%) compared to HRP/HRU cases (19/69, 27.5%, p = 0.0012). Median Recurrence-Free Survival (RFS) was 35 months for HRD cases and 225 months for HRP/HRU cases (p = 0.001). At 2 years, there were 60% HRD cases and 88% HRP/HRU cases recurrence-free. At 5 years there were 29% HRD and 69% HRP/HRU cases recurrence-free (p = 0.001). Conclusions: Despite a high rate of complete surgical staging and six cycles of adjuvant chemotherapy, recurrence rate was high in this early-stage cohort. Higher recurrence rates were seen in the HRD group, however these data are likely biased by the clinical practice of tumor testing primarily at the time of recurrence rather than the upfront setting. RFS was significantly lower for HRD cases.

Use of the Khorana score to predict venous thromboembolism in patients undergoing chemotherapy for uterine cancer.

Objective: Gynecologic cancers are associated with a high risk of venous thromboembolism (VTE). The Khorana score is a validated tool to assess risk of VTE in cancer patients. The purpose of this study is to determine if the Khorana score can be used as a risk stratification tool for VTE in patients with uterine cancer undergoing chemotherapy. Methods: A retrospective cohort study of patients with newly diagnosed uterine cancer receiving chemotherapy over a 4-year period was conducted. The patients were stratified based on their Khorana score as well as their chemotherapy sequence, neoadjuvant or definitive versus adjuvant. Results: A total of 276 patients were included: 40 received neoadjuvant or definitive, 236 adjuvant chemotherapy. Most patients had advanced stage disease (64.5%). 18 (6.5%) patients developed VTE within 180 days of initiating chemotherapy. High Khorana score was associated with a non-significant increase in VTE (K ≥ 2 OR 1.17, CI 0.40-3.39, K ≥ 3 OR 1.69, CI 0.61-4.69) but had poor predictive accuracy based on area under the curve (K ≥ 2 0.51, K ≥ 3 0.55). The VTE rate was higher in the neoadjuvant/definitive chemotherapy group to adjuvant (12.5% vs 5.5%, p = 0.11). While the former group had a higher average Khorana score (2.35 vs 1.93, p = 0.0048), this was not predictive of VTE. Conclusions: While validated in other cancer types, the Khorana score was found to be a poor predictor of VTE in patients with uterine cancer. The use of the Khorana score to guide routine thromboprophylaxis in these patients should be used with caution and further investigation is warranted.

Do Not Forget about Hormonal Therapy for Recurrent Endometrial Cancer: A Review of Options, Updates, and New Combinations.

Hormonal therapy has long been a treatment modality for recurrent endometrial cancer. It is appealing for patients with low-grade, slow-growing tumors or in patients for which other treatment types may be too toxic. Hormonal therapy is well tolerated and has response rates ranging from 9 to 33%. Hormonal treatment options take advantage of the estrogen-dependent molecular pathways in endometrial cancers. Current options for hormonal therapies include progesterone therapy (medroxyprogesterone acetate and megestrol acetate) as a single agent or in combination and agents that target the estrogen pathway. Aromatase inhibitors have had modest single-agent activity, but synergistic effects have been found when used in combination with targeted therapy including mTOR inhibitors and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. Molecular profiling of endometrial cancers has begun to help individualize treatments. This review will report on existing data and ongoing trials investigating novel hormonal therapy agents.

Postoperative venous thromboembolism risk stratification in patients with uterine cancer.

BACKGROUND: Uterine cancers are associated with a high risk for venous thromboembolisms. The American Society of Clinical Oncology practice guidelines recommend that all patients undergoing pelvic surgery for cancer should receive extended pharmacologic thromboprophylaxis with the duration being dependent on risk. However, risk stratification for patients with uterine cancer is not clearly defined. The Caprini score is the most widely used risk assessment model but it has been found to have limited use in the gynecologic oncology population. A modified Caprini score has been explored in other populations. The Khorana score is an additional risk assessment model that has not been studied in this context. OBJECTIVE: Our objective was to evaluate the ability of a modified Caprini model and the Khorana score to risk stratify patients with uterine cancer for postoperative venous thromboembolisms within 90 days of surgery. STUDY DESIGN: Following institutional review board approval, a retrospective cohort study was performed, and all patients with uterine cancer who underwent a hysterectomy over a 4-year period were included. The Caprini and Khorana scores were calculated for each patient. The Caprini score cutoff for highest risk was evaluated at ≥7, ≥8, and ≥9 (modified Caprini) and the Khorana score cutoff was evaluated at ≥2 and ≥3. To determine the prognostic use of each score and other clinico-pathologic criteria related to the development of a venous thromboembolism, univariate analyses were performed using independent t tests, chi-square tests, or Fisher's exact tests; a multivariate analysis was performed using logistic regression. RESULTS: A total of 954 patients were included. The rate of venous thromboembolism development was 1.7% (16/954). A minimally invasive surgical approach was used in 90.5% (863/954) of patients. The mean Caprini score for patients with a venous thromboembolism was 10.3 compared with 8.1 for patients without a venous thromboembolism (95% confidence interval, 1.17-3.33; P<.0001). The mean Khorana score for the venous thromboembolism group was 2.4 vs 1.9 for those without (95% confidence interval, 0.04-0.82; P=.03). Both the Caprini and Khorana scores were found to be associated with venous thromboembolisms, but only a Caprini score with a cutoff of ≥8 or ≥9 was statistically significant (risk ratio, 31.25; 95% confidence interval, 1.88-519.49; risk ratio, 4.59; 95% confidence interval, 1.49-14.13, respectively), with high accuracy based on the area under the curve (0.75 and 0.68, respectively). Of the minimally invasive subgroup, 11.7% (101/863) of patients had same-day discharge with no postoperative thromboprophylaxis; none of these patients developed venous thromboembolisms. Despite extended prophylaxis among the laparotomy patients (30 days), the rate of venous thromboembolisms was more than 3 times that of the minimally invasive group (5.49% vs 1.7%). Advanced tumor stage and leukocytosis were noted to be independent risk factors for venous thromboembolisms. CONCLUSION: Our study suggests that using a modified Caprini score could help to identify the highest-risk patients who would benefit from prolonged thromboprophylaxis, could reduce the incidence of postoperative venous thromboembolisms, and could minimize the cost and harm of overtreatment. These findings need to be validated in a prospective manner, and further research is needed to determine the optimal duration of therapy.

[Substance use among older residents in residential and long-term care facilities: A scoping review on intervention practices]. / Consommation de substances psychoactives chez les résident(e)s fréquentant des milieux d'hébergement et de soins de longue durée pour personnes âgées en perte d'autonomie : une revue de la portée sur les pratiques d'intervention.

Objectives Residential and long-term care facilities struggle to support older residents who experience a loss of autonomy, use psychoactive substances and face issues related to their consumption. Substance use can interact negatively with other physical, mental health or social conditions (e.g., homelessness) to create particularly complex profiles. In Quebec, as in many other countries around the world, there are often no clear guidelines for the care of elderly residents using psychoactive substances. The purpose of this study is to document the characteristics of existing interventions and practices towards older people who use psychoactive substances in residential and long-term care facilities in order to support decision makers with improvement of services and quality of care. Methods We carried out a scoping review of the scientific literature. We consulted 7 scientific databases (MEDLINE, EmBASE, PsychINFO, CINAHL, SocIndex, Ageline, Érudit). To identify the relevant grey literature, we explored the websites of governmental, non-governmental organizations and professional associations in the fields of addiction and aging in a selection of OECD countries. In addition, 31 experts were solicited to enhance the documentary research process. We conducted a thematic analysis on 65 documents. Results The philosophies underlying practices related to substance use reflect a hard balance to strike between priorities to be given to health, safety, and respect for human rights in residential and long-term-care settings. These philosophies, and the practices that stem from them, are distributed along a continuum ranging from the demand for abstinence to a total "laissez-faire" approach to substance use. Services offered are varied and involve complementary expertise in the health and social fields to meet the complex needs of this population. Finally, a diversity of organizational dynamics is observed: proposed interventions regarding substance use can be structured programs, informal interventions, internal substance use management policies, or specific settings for older adults who use substances, such as wet eldercare facilities. Conclusion This portrait of the interventions that target the use of psychoactive substances in residential and long-term care settings may assist care workers and service managers in Quebec and internationally, with clinical practice improvements. This may ultimately support both seniors-dedicated and addiction services. In view of population aging and the complex needs of older populations, clear guidelines are crucial to ensure the quality of care and services in these settings.

Quasi-Entropy Closure: a fast and reliable approach to close the moment equations of the Chemical Master Equation.

MOTIVATION: The Chemical Master Equation is a stochastic approach to describe the evolution of a (bio)chemical reaction system. Its solution is a time-dependent probability distribution on all possible configurations of the system. As this number is typically large, the Master Equation is often practically unsolvable. The Method of Moments reduces the system to the evolution of a few moments, which are described by ordinary differential equations. Those equations are not closed, since lower order moments generally depend on higher order moments. Various closure schemes have been suggested to solve this problem. Two major problems with these approaches are first that they are open loop systems, which can diverge from the true solution, and second, some of them are computationally expensive. RESULTS: Here we introduce Quasi-Entropy Closure, a moment-closure scheme for the Method of Moments. It estimates higher order moments by reconstructing the distribution that minimizes the distance to a uniform distribution subject to lower order moment constraints. Quasi-Entropy Closure can be regarded as an advancement of Zero-Information Closure, which similarly maximizes the information entropy. Results show that both approaches outperform truncation schemes. Quasi-Entropy Closure is computationally much faster than Zero-Information Closure, although both methods consider solutions on the space of configurations and hence do not completely overcome the curse of dimensionality. In addition, our scheme includes a plausibility check for the existence of a distribution satisfying a given set of moments on the feasible set of configurations. All results are evaluated on different benchmark problems. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Beyond mismatch repair deficiency? Pre-treatment neutrophil-to-lymphocyte ratio is associated with improved overall survival in patients with recurrent endometrial cancer treated with immunotherapy.

OBJECTIVE: To determine the association of pre-treatment neutrophil-to-lymphocyte ratio (NLR) with progression-free survival (PFS) and overall survival (OS) for patients with recurrent endometrial cancer (EC) treated with immunotherapy. METHODS: Recurrent EC patients treated with immunotherapy alone or in combination from 2016 to 2021 were included. Demographics, pre-treatment laboratory results, pathologic data, response at first radiographic assessment, and cancer outcomes were obtained from the medical record. Kaplan-Meier curves were generated to compare PFS and OS stratified by NLR. RESULTS: The 106 patients included in the study were stratified by NLR <6 (n = 77, 72.6%) or NLR ≥6 (n = 29, 27.3%). Most had endometrioid pathology (59%), widely metastatic disease, and 36.8% had received ≥2 treatment lines before initiating immunotherapy. Mismatch repair deficiency (dMMR) was noted in 52 (49.1%) tumors. Most dMMR patients (94.3%) were treated with single-agent pembrolizumab, and most MMR proficient patients (78.7%) were treated with lenvatinb plus pembrolizumab. In the overall cohort, 40.2% (partial response (PR) 29.9%, complete response (CR) 10.4%) of patients with a NLR <6 responded at first radiographic assessment, compared to 31% (PR 27.5%, CR 3.4%) of patients with NLR ≥6 (p 0.691). Kaplan-Meier curves stratified by NLR <6 vs. ≥6 showed no difference in PFS. However, NLR <6 was associated with improved OS (p < 0.05). In the NLR < 6 group, the probability of survival at one year was 69% (95% CI: 58%, 82%), compared to 41% (95% CI: 26%, 67%) for the NLR > 6 group. CONCLUSIONS: Pre-treatment NLR <6 was associated with improved OS for recurrent EC patients treated with immunotherapy. NLR holds promise as a predictive biomarker for survival after immunotherapy treatment for patients with recurrent EC.

Aberrant expression of TMEM205 signaling promotes platinum resistance in ovarian cancer: An implication for the antitumor potential of DAP compound.

INTRODUCTION: TMEM205 is a novel transmembrane protein associated with platinum resistance (PR) in epithelial ovarian carcinoma (OC), however, the specific mechanisms associated with this resistance remain to be elucidated. METHODS: TMEM205 expression was evaluated in platinum-sensitive (PS) versus platinum resistant (PR) ovarian cancer cell lines and patient serum/tissues. Exosomal efflux of platinum was evaluated with inductively coupled plasma mass spectrometry (ICP-MS) after pre-treatment with small molecule inhibitors (L-2663/L-2797) of TMEM205 prior to treatment with platinum. Cytotoxicity of combination treatment was confirmed in vitro and in an in vivo model. RESULTS: TMEM205 expression was 10-20 fold higher in PR compared to PS ovarian cancer cell lines, serum samples, and tissues. Co-localization with CD1B was confirmed by in-situ proximity ligation assay suggesting that TMEM205 may mediate PR via the exosomal pathway. Exosomal secretion was significantly increased 5-10 fold in PR cell lines after treatment with carboplatin compared to PS cell lines. Pre-treatment with L-2663 prior to carboplatin resulted in significantly increased intracellular concentration of fluorescently-labeled cisplatin and decreased exosomal efflux of platinum. Decreased cell survival and tumor growth in vitro and in vivo was observed when PR cells were treated with a combination of L-2663 with carboplatin compared to carboplatin alone. CONCLUSION: TMEM205 appears to be involved in the development of PR in ovarian cancer through the exosomal efflux of platinum agents. This study provides pre-clinical evidence that TMEM205 could serve as a possible biomarker for PR as well as a therapeutic target in combination with platinum agents.

How do Past, Present and Future Weigh into Trajectories of Precarity? The Time Perspectives of Young Psychoactive Substance Users Living in Situations of Social Precarity in Montreal.

Young psychoactive substance users in social precarity are vulnerable to a range of health and social issues. Time perspective is one aspect to consider in supporting change. This study draws on the views expressed by young adults to portray their subjective experience of time, how this perception evolves and its implications for their substance use and socio-occupational integration trajectories. The sample includes 23 young psychoactive substance users (M = 24.65 years old; 83% male) in social precarity frequenting a community-based harm reduction centre. Thematic analysis of the interviews reveals the past to be synonymous with disappointment and disillusionment, but also a constructive force. Participants expressed their present-day material and human needs as well as their need for recognition and a sense of control over their own destiny. Their limited ability to project into the future was also discussed. Avenues on how support to this population might be adapted are suggested.

Problematic Substance Use, Help-Seeking, and Service Utilization Trajectories among Seniors: An Exploratory Qualitative Study.

Problematic substance use has a significant impact on the health of a large proportion of people aged 65 years and older. Along with population growth, there is an increase in seniors enrolling for treatment in Québec (Canada). This study explores the perspectives of older adults related to their substance use experiences, help-seeking and utilization of addiction treatment services. In-depth interviews were conducted with 11 seniors receiving addiction treatment in two area in Québec. Thematic analysis highlight that seniors' experiences, life contexts, and social participation influence their substance use. Help-seeking process can be triggered by realizing the extent of substance use, while barriers and facilitators shape this experience. Utilization of addiction treatment services was mainly perceived positively. Several characteristics and components of services enable seniors to have positive experiences. Substance use can be employed as an adaptation strategy to get through hardships or ease loneliness and boredom. Talking to people, such as family, friends or professionals, is important to older adults' developing trust and engaging in a process to change substance use habits. Based upon these results, clinical recommendations to take into account the complex needs of seniors seeking treatment and related to their social environment are formulated.

DNA sequence-dependent activity and base flipping mechanisms of DNMT1 regulate genome-wide DNA methylation.

DNA methylation maintenance by DNMT1 is an essential process in mammals but molecular mechanisms connecting DNA methylation patterns and enzyme activity remain elusive. Here, we systematically analyzed the specificity of DNMT1, revealing a pronounced influence of the DNA sequences flanking the target CpG site on DNMT1 activity. We determined DNMT1 structures in complex with preferred DNA substrates revealing that DNMT1 employs flanking sequence-dependent base flipping mechanisms, with large structural rearrangements of the DNA correlating with low catalytic activity. Moreover, flanking sequences influence the conformational dynamics of the active site and cofactor binding pocket. Importantly, we show that the flanking sequence preferences of DNMT1 highly correlate with genomic methylation in human and mouse cells, and 5-azacytidine triggered DNA demethylation is more pronounced at CpG sites with flanks disfavored by DNMT1. Overall, our findings uncover the intricate interplay between CpG-flanking sequence, DNMT1-mediated base flipping and the dynamic landscape of DNA methylation.

Differential DNA methylation in high-grade serous ovarian cancer (HGSOC) is associated with tumor behavior.

The epigenome offers an additional facet of cancer that can help categorize patients into those at risk of disease, recurrence, or treatment failure. We conducted a retrospective, nested, case-control study of advanced and recurrent high-grade serous ovarian cancer (HGSOC) patients in which we assessed epigenome-wide association using Illumina methylationEPIC arrays to characterize DNA methylation status and RNAseq to evaluate gene expression. Comparing HGSOC tumors with normal fallopian tube tissues we observe global hypomethylation but with skewing towards hypermethylation when interrogating gene promoters. In total, 5,852 gene interrogating probes revealed significantly different methylation. Within HGSOC, 57 probes highlighting 17 genes displayed significant differential DNA methylation between primary and recurrent disease. Between optimal vs suboptimal surgical outcomes 99 probes displayed significantly different methylation but only 29 genes showed an inverse correlation between methylation status and gene expression. Overall, differentially methylated genes point to several pathways including RAS as well as hippo signaling in normal vs primary HGSOC; valine, leucine, and isoleucine degradation and endocytosis in primary vs recurrent HGSOC; and pathways containing immune driver genes in optimal vs suboptimal surgical outcomes. Thus, differential DNA methylation identified numerous genes that could serve as potential biomarkers and/or therapeutic targets in HGSOC.

Effects of a blocked versus an alternated sequence of balance and plyometric training on physical performance in youth soccer players.

BACKGROUND: The sequence of blocked balance training (BT) followed by blocked plyometric training (PT) showed greater improvements in physical performance than vice versa and is explained by a preconditioning effect of BT-related adaptations on subsequent adaptations induced by PT. However, it remains unclear whether beneficial effects can also be induced using alternating instead of blocked BT and PT exercise sequences. Thus, we examined the effects of a blocked versus an alternated sequence of BT and PT on physical performance in trained individuals. METHODS: Twenty young soccer players (13 years) were randomly assigned to a blocked (n = 10) or an alternated (n = 10) intervention group. Both groups trained balance and plyometric exercises for six weeks (two sessions/week). The exercises were conducted in a blocked (three weeks of BT followed by three weeks of PT) or an alternated sequence (weekly change of BT and PT). Assessment of pre- and post-training performance included measures of balance, muscle power, speed, and agility. RESULTS: Mainly significant main effects of Test (i.e., pre- to post-test improvements) were observed for the Y-balance test (p ≤ 0.014, 1.3 ≤ Cohen's d ≤ 1.81), the squat jump (p = 0.029, d = 1.36), the countermovement jump (p = 0.002, d = 2.21), the drop jump (p = 0.004, d = 1.96), the split times/total time over 15-m sprinting (p ≤ 0.001, 2.02 ≤ d ≤ 3.08), and the figure-T agility run (p < 0.001, d = 3.80). Further, tendencies toward significant Test x Group interactions were found for several items of the Y-balance test and for SJ height in favor of the blocked BTPT group. CONCLUSIONS: Our results indicate that the combined training of balance and plyometric exercises is effective to improve proxies of physical performance in youth soccer players. In addition, there is a limited advantage in some parameters of balance and muscle power for the blocked as compared to the alternated sequence of BT and PT.

hCG production by mucinous adenocarcinoma of the ovary in a reproductive aged woman.

When elevated serum hCG is discovered during the work up of a gynecologic tumor, it is paramount to identify the source of hCG prior to initiation of treatment. Potential sources of hCG include viable intrauterine pregnancy, ectopic pregnancy, miscarriage, gestational trophoblastic disease, pituitary hCG production, phantom hCG (heterophilic antibody interference), and tumor production. Here, we present a case of elevated hCG in a young women with a large complex pelvic mass. Prior to treatment initiation, the patient underwent work up for hCG elevation, which was ultimately found to be from tumor production. Pathologic examination revealed the mass to be a mucinous adenocarcinoma of the ovary with aberrant expression of hCG, rather than the more typical hCG producing germ cell tumor. We detail the preoperative evaluation process of hCG elevation. Additionally, we discuss the role of hCG in ovarian cancer and influence on tumorigenesis and management.