HReMAS: Hybrid Real-time Musical Alignment System

[EN] This paper presents a real-time audio-to-score alignment system for musical applications. The aim of these systems is to synchronize a live musical performance with its symbolic representation in a music sheet. We have used as a base our previous real-time alignment system by enhancing it with a traceback stage, a stage used in offline alignment to improve the accuracy of the aligned note. This stage introduces some delay, what forces to assume a trade-off between output delay and alignment accuracy that must be considered in the design of this type of hybrid techniques. We have also improved our former system to execute faster in order to minimize this delay. Other interesting improvements, like identification of silence frames, have also been incorporated to our proposed system.This work has been supported by the "Ministerio de Economia y Competitividad" of Spain and FEDER under Projects TEC2015-67387-C4-{1,2,3}-R.Cabañas-Molero, P.; Cortina-Parajón, R.; Combarro, EF.; Alonso-Jordá, P.; Bris-Peñalver, FJ. (2019). HReMAS: Hybrid Real-time Musical Alignment System. The Journal of Supercomputing. 75(3):1001-1013. https://doi.org/10.1007/s11227-018-2265-1S10011013753Alonso P, Cortina R, Rodríguez-Serrano FJ, Vera-Candeas P, Alonso-González M, Ranilla J (2017) Parallel online time warping for real-time audio-to-score alignment in multi-core systems. J Supercomput 73(1):126–138Alonso P, Vera-Candeas P, Cortina R, Ranilla J (2017) An efficient musical accompaniment parallel system for mobile devices. J Supercomput 73(1):343–353Arzt A (2016) Flexible and robust music tracking. Ph.D. thesis, Johannes Kepler University Linz, Linz, ÖsterreichArzt A, Widmer G, Dixon S (2008) Automatic page turning for musicians via real-time machine listening. In: Proceedings of the 18th European Conference on Artificial Intelligence (ECAI), Amsterdam, pp 241–245Carabias-Orti J, Rodríguez-Serrano F, Vera-Candeas P, Ruiz-Reyes N, Cañadas-Quesada F (2015) An audio to score alignment framework using spectral factorization and dynamic time warping. In: Proceedings of ISMIR, pp 742–748Cont A (2006) Realtime audio to score alignment for polyphonic music instruments, using sparse non-negative constraints and hierarchical HMMs. In: 2006 IEEE International Conference on Acoustics Speech and Signal Processing Proceedings, vol 5. pp V–VCont A, Schwarz D, Schnell N, Raphael C (2007) Evaluation of real-time audio-to-score alignment. In: International Symposium on Music Information Retrieval (ISMIR), ViennaDannenberg RB, Raphael C (2006) Music score alignment and computer accompaniment. Commun ACM 49(8):38–43Devaney J, Ellis D (2009) Handling asynchrony in audio-score alignment. In: Proceedings of the International Computer Music Conference Computer Music Association. pp 29–32Dixon S (2005) An on-line time warping algorithm for tracking musical performances. In: Proceedings of the International Joint Conference on Artificial Intelligence (IJCAI). pp 1727–1728Duan Z, Pardo B (2011) Soundprism: an online system for score-informed source separation of music audio. IEEE J Sel Top Signal Process 5(6):1205–1215Ewert S, Muller M, Grosche P (2009) High resolution audio synchronization using chroma onset features. In: IEEE International Conference on Acoustics, Speech and Signal Processing, 2009 (ICASSP 2009). pp 1869–1872Hu N, Dannenberg R, Tzanetakis G (2003) Polyphonic audio matching and alignment for music retrieval. In: 2003 IEEE Workshop on Applications of Signal Processing to Audio and Acoustics. pp 185–188Kaprykowsky H, Rodet X (2006) Globally optimal short-time dynamic time warping, application to score to audio alignment. In: Proceedings of the International Conference on Acoustics, Speech and Signal Processing, vol 5. pp. V–VLi B, Duan Z (2016) An approach to score following for piano performances with the sustained effect. IEEE/ACM Trans Audio Speech Lang Process 24(12):2425–2438Miron M, Carabias-Orti JJ, Bosch JJ, Gómez E, Janer J (2016) Score-informed source separation for multichannel orchestral recordings. J Electr Comput Eng 2016(8363507):1–19Muñoz-Montoro A, Cabañas-Molero P, Bris-Peñalver F, Combarro E, Cortina R, Alonso P (2017) Discovering the composition of audio files by audio-to-midi alignment. In: Proceedings of the 17th International Conference on Computational and Mathematical Methods in Science and Engineering. pp 1522–1529Orio N, Schwarz D (2001) Alignment of monophonic and polyphonic music to a score. In: Proceedings of the International Computer Music Conference (ICMC), pp 155–158Pätynen J, Pulkki V, Lokki T (2008) Anechoic recording system for symphony orchestra. Acta Acust United Acust 94(6):856–865Raphael C (2010) Music plus one and machine learning. In: Proceedings of the 27th International Conference on Machine Learning (ICML), pp 21–28Rodriguez-Serrano FJ, Carabias-Orti JJ, Vera-Candeas P, Martinez-Munoz D (2016) Tempo driven audio-to-score alignment using spectral decomposition and online dynamic time warping. ACM Trans Intell Syst Technol 8(2):22:1–22:2

Response-adapted treatment with rituximab, bendamustine, mitoxantrone, and dexamethasone followed by rituximab maintenance in patients with relapsed or refractory follicular lymphoma after first-line immunochemotherapy: Results of the RBMDGELTAMO08 phase II trial

Background Consensus is lacking regarding the optimal salvage therapy for patients with follicular lymphoma who relapse after or are refractory to immunochemotherapy. Methods This phase II trial evaluated the efficacy and safety of response-adapted therapy with rituximab, bendamustine, mitoxantrone, and dexamethasone (RBMD) in follicular lymphoma patients who relapsed after or were refractory to first-line immunochemotherapy. Sixty patients received three treatment cycles, and depending on their response received an additional one (complete/unconfirmed complete response) or three (partial response) cycles. Patients who responded to induction received rituximab maintenance therapy for 2 years. Results Thirty-three (55%) and 42 (70%) patients achieved complete/unconfirmed complete response after three cycles and on completing induction therapy (4-6 cycles), respectively (final overall response rate, 88.3%). Median progression-free survival was 56.4 months (median follow-up, 28.3 months; 95% CI, 15.6-51.2). Overall survival was not reached. Progression-free survival did not differ between patients who received four vs six cycles (P = .6665), nor between patients who did/did not receive rituximab maintenance after first-line therapy (P = .5790). Median progression-free survival in the 10 refractory patients was 25.5 months (95% CI, 0.6-N/A) and was longer in patients who had shown progression of disease after 24 months of first-line therapy (median, 56.4 months; 95% CI, 19.8-56.4) than in those who showed early progression (median, 42.31 months; 95% CI, 24.41-NA) (P = .4258). Thirty-six (60%) patients had grade 3/4 neutropenia. Grade 3/4 febrile neutropenia and infection were recorded during induction (4/60 [6.7%] and 5/60 [8.3%] patients, respectively) and maintenance (2/43 [4.5%] and 4/43 [9.1%] patients, respectively). Conclusions This response-adapted treatment with RBMD followed by rituximab maintenance is an effective and well-tolerated salvage treatment for relapsed/refractory follicular lymphoma following first-line immunochemotherapy

Natural History of MYH7-Related Dilated Cardiomyopathy

BACKGROUND: Variants in myosin heavy chain 7 (MYH7) are responsible for disease in 1% to 5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described. OBJECTIVE: We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression. METHODS: We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% female; 35.6 ± 19.2 years) recruited from 29 international centers. RESULTS: At initial evaluation, 106 (72.1%) patients had DCM (left ventricular ejection fraction: 34.5% ± 11.7%). Median follow-up was 4.5 years (IQR: 1.7-8.0 years), and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years of age. Thirty-six percent of patients with DCM met imaging criteria for LV noncompaction. During follow-up, 28% showed left ventricular reverse remodeling. Incidence of adverse cardiac events among patients with DCM at 5 years was 11.6%, with 5 (4.6%) deaths caused by end-stage heart failure (ESHF) and 5 patients (4.6%) requiring heart transplantation. The major ventricular arrhythmia rate was low (1.0% and 2.1% at 5 years in patients with DCM and in those with LVEF of ≤35%, respectively). ESHF and major ventricular arrhythmia were significantly lower compared with LMNA-related DCM and similar to DCM caused by TTN truncating variants. CONCLUSIONS: MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare

Nuclear Translocation of Glutaminase GLS2 in Human Cancer Cells Associates with Proliferation Arrest and Differentiation.

Glutaminase (GA) catalyzes the first step in mitochondrial glutaminolysis playing a key role in cancer metabolic reprogramming. Humans express two types of GA isoforms: GLS and GLS2. GLS isozymes have been consistently related to cell proliferation, but the role of GLS2 in cancer remains poorly understood. GLS2 is repressed in many tumor cells and a better understanding of its function in tumorigenesis may further the development of new therapeutic approaches. We analyzed GLS2 expression in HCC, GBM and neuroblastoma cells, as well as in monkey COS-7 cells. We studied GLS2 expression after induction of differentiation with phorbol ester (PMA) and transduction with the full-length cDNA of GLS2. In parallel, we investigated cell cycle progression and levels of p53, p21 and c-Myc proteins. Using the baculovirus system, human GLS2 protein was overexpressed, purified and analyzed for posttranslational modifications employing a proteomics LC-MS/MS platform. We have demonstrated a dual targeting of GLS2 in human cancer cells. Immunocytochemistry and subcellular fractionation gave consistent results demonstrating nuclear and mitochondrial locations, with the latter being predominant. Nuclear targeting was confirmed in cancer cells overexpressing c-Myc- and GFP-tagged GLS2 proteins. We assessed the subnuclear location finding a widespread distribution of GLS2 in the nucleoplasm without clear overlapping with specific nuclear substructures. GLS2 expression and nuclear accrual notably increased by treatment of SH-SY5Y cells with PMA and it correlated with cell cycle arrest at G2/M, upregulation of tumor suppressor p53 and p21 protein. A similar response was obtained by overexpression of GLS2 in T98G glioma cells, including downregulation of oncogene c-Myc. Furthermore, human GLS2 was identified as being hypusinated by MS analysis, a posttranslational modification which may be relevant for its nuclear targeting and/or function. Our studies provide evidence for a tumor suppressor role of GLS2 in certain types of cancer. The data imply that GLS2 can be regarded as a highly mobile and multilocalizing protein translocated to both mitochondria and nuclei. Upregulation of GLS2 in cancer cells induced an antiproliferative response with cell cycle arrest at the G2/M phase