THE EFFECTS OF ATTENTIONAL FOCUS ON THE PERFORMANCE OF VOLLEYBALL JUMP SERVE IN ELITE PLAYERS

Evidence of the last few years demonstrated that the far external focus of attention would lead to better motor performance (e.g., Mc Nevin., et al, 2003; MacKay and Wulf, 2012). According to the Frequency of Movement Adjustment analysis evidence of “Constrained Action Hypothesis”, the aim of this study was to examine the effects of different attentional focuses on the performance of a manipulative-complex motor skill in highly skillful athletes. 12 professional volleyball players completed a 4 blocks of 8 trail (4 trail for accuracy, 4 trail for effectiveness) of jump serve in four experimental conditions (Non-Instruction, Internal focuses on hand movement, Near external focuses on ball, and Far external focuses on target zone or player). The data of accuracy, effectiveness, and self-perception of the performance was acquired by pointed target areas, analyzing volleyball serve effectiveness method, and self-rated manipulative check, respectively. Results of ANOVA with repeated measures showed that accuracy scores, effectiveness, and self-perceived performance of volleyball jump serve in far external condition was better than near external and internal conditions. In addition, the significant differences between non-instructional and far external conditions were observed only in self-perceived performance. In general, these results confirmed recent findings regarding the detrimental effects of internal focus of attention and the facilitative effects of external focus of attention, especially far external on skilled performance.   Article visualizations

The Status of the Concept of Atmosphere in Hermann Schmitz’s New Phenomenology

This paper seeks to analyse the concept of atmosphere in the philosophical system of Hermann Schmitz, the founder of New Phenomenology, as a fundamental concept for understanding his philosophical system; he uses this concept to transcend the duality of subject-object as well as to show the hidden realities and the foundations of lived experience of reality, by looking at how phenomenological analysis is revealed. Beside being used in sciences such as physics, meteorology, and psychology, the term also refers to the atmosphere as a concrete phenomenon; it is also an evidence of his understanding the phenomenology and reformulating it. This paper aims to show the connection between the concept of the felt-body (Leib), as the theoretical core of his work, and space and emotion as other key concepts in his philosophical system, by using the structural analysis of the concept and the phenomen of atmosphere.The result of the analysis in this paper shows the special place of the concept of atmosphere in Schmitz's philosophical system and its prominent role in establishing his method of New Phenomenology

Two-Dimensional Transition Metal Dichalcogenide as Electron Transport Layer of Perovskite Solar Cells

Conventional perovskite solar cells utilize a combination of a compact and mesoporous layer of TiO2 or SnO2 as the electron transport layer. This structure is vulnerable to massive loss of photogenerated carriers due to grain boundary resistance in the layer. In this chapter, we will discuss a potential electron transport layer that might drive higher power conversion efficiency, i.e., thin and single-crystalline 2D transition metal dichalcogenide. Because of their ultimate thin structure, they facilitate rapid electron transport and enhanced carrier extraction in the solar cells device. We will also discuss the current state of the art of 2D transition metal dichalcogenide atomic layer application as an electron transport layer in the perovskite solar cells as well as our recent attempt in this field

Clinical Findings of Sydenham Chorea in Pediatric Patients: A Single-Center Retrospective Study

Purpose Sydenham chorea is known for its rapid, irregular, and aimless involuntary movements and is considered a benign and self-limiting condition among the major manifestations of rheumatic fever. The current study reviewed the demographic, clinical, and paraclinical findings of pediatric patients with Sydenham chorea. Methods This cross-sectional study was conducted among 22 patients with Sydenham chorea who were admitted to the pediatric wards of Mashhad Imam Reza and Ghaem Hospitals between 2006 and 2016. Data from these patients’ medical records were extracted, organized using checklist forms, and analyzed. Results Eight patients were male and 14 were female. The average age was 10.09±3.53 years. In 31.8% of patients, chorea was the only sign of rheumatic fever. Chorea was unilateral in 21.1% of patients. The most common clinical findings were, in descending order, jerky movements, facial grimacing, gait disorders, mental disorders, speech disorders, muscle weakness, and milkmaid's grip. Cardiac auscultation was normal in 76.2% of patients, while a holosystolic murmur was heard in 23.8%. In laboratory exams, 50% of patients were erythrocyte sedimentation rate (ESR)-positive, 31.2% were C-reactive protein (CRP)-positive, and 53.3% were anti-streptolysin O (ASO)-positive. Echocardiography showed the prevalence of mitral regurgitation (63.6%), aortic regurgitation (45.5%), tricuspid regurgitation (22.7%), pulmonary regurgitation (4.5%), and pericardial effusion (4.5%). Conclusion This study showed that Sydenham chorea can be the only sign of rheumatic fever. This disease typically occurs in children between the ages of 7 and 12. ESR, CRP, and ASO can be the most effective laboratory tests for diagnosis

Enhancing cardiac assessments: accurate and efficient prediction of quantitative fractional flow reserve

BackgroundObstruction within the left anterior descending coronary artery (LAD) is prevalent, serving as a prominent and independent predictor of mortality. Invasive Fractional flow reserve (FFR) is the gold standard for Coronary Artery Disease risk assessment. Despite advances in computational and imaging techniques, no definitive methodology currently assures clinicians of reliable, non-invasive strategies for future planning.MethodThe present research encompassed a cohort of 150 participants who were admitted to the Rajaie Cardiovascular, Medical, and Research Center. The method includes a three-dimensional geometry reconstruction, computational fluid dynamics simulations, and methodology optimization for the computation time. Four patients are analyzed within this study to showcase the proposed methodology. The invasive FFR results reported by the clinic have validated the optimized model.ResultsThe computational FFR data derived from all methodologies are compared with those reported by the clinic for each case. The chosen methodology has yielded virtual FFR values that exhibit remarkable proximity to the clinically reported patient-specific FFR values, with the MSE of 6.186e-7 and R2 of 0.99 (p = 0.00434).ConclusionThis approach has shown reliable results for all 150 patients. The results are both computationally and clinically user-friendly, with the accumulative pre and post-processing time of 15 min on a desktop computer (Intel i7 processor, 16 GB RAM). The proposed methodology has the potential to significantly assist clinicians with diagnosis

Randomized Phase II Trial of Dendritic Cell/Myeloma Fusion Vaccine with Lenalidomide Maintenance after Upfront Autologous Hematopoietic Cell Transplantation for Multiple Myeloma: BMT CTN 1401.

PURPOSE: Vaccination with dendritic cell (DC)/multiple myeloma (MM) fusions has been shown to induce the expansion of circulating multiple myeloma-reactive lymphocytes and consolidation of clinical response following autologous hematopoietic cell transplant (auto-HCT). PATIENTS AND METHODS: In this randomized phase II trial (NCT02728102), we assessed the effect of DC/MM fusion vaccination, GM-CSF, and lenalidomide maintenance as compared with control arms of GM-CSF and lenalidomide or lenalidomide maintenance alone on clinical response rates and induction of multiple myeloma-specific immunity at 1-year posttransplant. RESULTS: The study enrolled 203 patients, with 140 randomized posttransplantation. Vaccine production was successful in 63 of 68 patients. At 1 year, rates of CR were 52.9% (vaccine) and 50% (control; P = 0.37, 80% CI 44.5%, 61.3%, and 41.6%, 58.4%, respectively), and rates of VGPR or better were 85.3% (vaccine) and 77.8% (control; P = 0.2). Conversion to CR at 1 year was 34.8% (vaccine) and 27.3% (control; P = 0.4). Vaccination induced a statistically significant expansion of multiple myeloma-reactive T cells at 1 year compared with before vaccination (P = 0.024) and in contrast to the nonvaccine arm (P = 0.026). Single-cell transcriptomics revealed clonotypic expansion of activated CD8 cells and shared dominant clonotypes between patients at 1-year posttransplant. CONCLUSIONS: DC/MM fusion vaccination with lenalidomide did not result in a statistically significant increase in CR rates at 1 year posttransplant but was associated with a significant increase in circulating multiple myeloma-reactive lymphocytes indicative of tumor-specific immunity. Site-specific production of a personalized cell therapy with centralized product characterization was effectively accomplished in the context of a multicenter cooperative group study. See related commentary by Qazilbash and Kwak, p. 4703

Identification of Long Non‐Coding RNAs Deregulated in Multiple Myeloma Cells Resistant to Proteasome Inhibitors

While the clinical benefit of proteasome inhibitors (PIs) for multiple myeloma (MM) treatment remains unchallenged, dose‐limiting toxicities and the inevitable emergence of drug resistance limit their long‐term utility. Disease eradication is compromised by drug resistance that is either present de novo or therapy‐induced, which accounts for the majority of tumor relapses and MM‐related deaths. Non‐coding RNAs (ncRNAs) are a broad class of RNA molecules, including long non‐coding RNAs (lncRNAs), that do not encode proteins but play a major role in regulating the fundamental cellular processes that control cancer initiation, metastasis, and therapeutic resistance. While lncRNAs have recently attracted significant attention as therapeutic targets to potentially improve cancer treatment, identification of lncRNAs that are deregulated in cells resistant to PIs has not been previously addressed. We have modeled drug resistance by generating three MM cell lines with acquired resistance to either bortezomib, carfilzomib, or ixazomib. Genome‐wide profiling identified lncRNAs that were significantly deregulated in all three PIresistant cell lines relative to the drug‐sensitive parental cell line. Strikingly, certain lncRNAs deregulated in the three PI‐resistant cell lines were also deregulated in MM plasma cells isolated from newly diagnosed patients compared to healthy plasma cells. Taken together, these preliminary studies strongly suggest that lncRNAs represent potential therapeutic targets to prevent or overcome drug resistance. More investigations are ongoing to expand these initial studies in a greater number of MM patients to better define lncRNAs signatures that contribute to PI resistance in MM

Abstract LB-245: Systems-based pharmacogenomics reveals that the ubiquitin ligase SCF-SKP2 is a molecular determinant of clinical response to bortezomib-based therapy

Abstract The molecular events that dictate the initiation, progression and therapeutic response in multiple myeloma (MM) remain incompletely understood. The ubiquitin (Ub) ligase Skp1-Cullin-1-Skp2 (SCFSkp2) complex promotes proliferation by inducing proteasomal degradation of the cyclin-dependent kinase inhibitor p27Kip1. Skp2 overexpression and reduced p27 levels are frequent events in human cancers and are associated with poor prognosis. Methods: Prospective pharmacogenomics was performed using next generation exome sequencing gene expression profiles (GEPs) compiled from the APEX/SUMMIT phase III clinical trial deposited in dataset GSE9782. 255 relapsed MM patients were randomized to bortezomib (BTZ) vs. dexamethasone (DEX) alone and progression-free (PFS) and overall survival (OS) then correlated with the pre-treatment GEPs. RPMI8226 cells were exposed for 8 months to successively escalated doses of the proteasome inhibitors BTZ, carfilzomib or ixazomib to generate chemoresistant cell lines. Side population (SP) cells were isolated from MMCLs and patients’ samples by flow cytometry sorting based upon Hoechst 33342 staining. Results: Pharmacogenomic correlation of GEPs with clinical response revealed hyperexpression of CUL1 and SKP2 in tumors from MM patients that did not respond to BTZ. CUL1 and SKP2 hyperexpression was correlated with significantly reduced PFS and OS after treatment with BTZ but not with DEX. Cullin-1 and Skp2 were elevated in cells generated with acquired PI-resistance. CUL1 or SKP2 genetic ablation significantly enhanced the sensitivity of chemoresistant cells to PIs. A high-throughput assay was then employed using GFP-tagged p27 to screen large databases and chemical libraries in order to identify novel lead compounds that inhibited the Skp2-dependent ubiquitination of p27. Treatment with DT204, a novel lead compound identified here, reduced p27 ubiquitination, its accumulation in myeloma cells and impaired Skp2 association with Cullin-1 and Cks1, a critical rate-limiting effector of Skp2 activity. The anti-myeloma effect of DT204 was diminished using a phosphorylation-defective p27 mutant. Co-treatment with DT204 enhanced the anti-myeloma effect of BTZ against MM cell lines, patient tumor cells, stem cells and the tumor-initiating clonogenic side population (SP). The in-vivo efficacy and survival benefit of DT204 as monotherapy or in combination with BTZ will be reported. Conclusion: Taken together, the results demonstrate that pharmacologics to selectively disrupt the SCFSkp2 complex-p27 axis within the UPS holds promise to overcome chemoresistance with therapeutic benefit for myeloma patients. Skp2, Cullin1 can be utilized as biomarkers to select MM patients who will benefit from early experimental therapeutics of Skp2-inhibitors. Note: This abstract was not presented at the meeting. Citation Format: Ehsan Malek, Mohamed Abdel Malek, James J. Driscoll. Systems-based pharmacogenomics reveals that the ubiquitin ligase SCF-SKP2 is a molecular determinant of clinical response to bortezomib-based therapy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-245. doi:10.1158/1538-7445.AM2015-LB-245</jats:p