Overlapped speech and music segmentation using singular spectrum analysis and random forests

Recent years have seen ever-increasing volumes of digital media archives and an enormous amount of user-contributed content. As demand for indexing and searching these resources has increased, and new technologies such as multimedia content management systems, en-hanced digital broadcasting, and semantic web have emerged, audio information mining and automated metadata generation have received much attention. Manual indexing and metadata tagging are time-consuming and subject to the biases of individual workers. An automated architecture able to extract information from audio signals, generate content-related text descriptors or metadata, and enable further information mining and searching would be a tangible and valuable solution. In the field of audio classification, audio signals may be broadly divided into speech or music. Most studies, however, neglect the fact that real audio soundtracks may have either speech or music, or a combination of the two, and this is considered the major hurdle to achieving high performance in automatic audio classification, since overlapping can contaminate relevant characteristics and features, causing incorrect classification or information loss. This research undertakes an extensive review of the state of the art by outlining the well-established audio features and machine learning techniques that have been applied in a broad range of audio segmentation and recognition areas. Audio classification systems and the suggested solutions for the mixed soundtracks problem are presented. The suggested solutions can be listed as follows: developing augmented and modified features for recognising audio classes even in the presence of overlaps between them; robust segmentation of a given overlapped soundtrack stream depends on an innovative method of audio decomposition using Singular Spectrum Analysis (SSA) that has been studied extensively and has received increasing attention in the past two decades as a time series decomposition method with many applications; adoption and development of driven classification methods; and finally a technique for continuous time series tasks. In this study, SSA has been investigated and found to be an efficient way to discriminate speech/music in mixed soundtracks by two different methods, each of which has been developed and validated in this research. The first method serves to mitigate the overlapping ratio between speech and music in the mixed soundtracks by generating two new soundtracks with a lower level of overlapping. Next, feature space is calculated for the output audio streams, and these are classified using random forests into either speech or music. One of the distinct characteristics of this method is the separation of the speech/music key features that lead to improve the classification performance. Nevertheless, that did encounter a few obstructions, including excessively long processing time, increased storage requirements (each frame symbolised by two outputs), and this all leads to greater computational load than previously. Meanwhile, the second method em-ploys the SSA technique to decompose a given audio signal into a series of Principal Components (PCs), where each PC corresponds to a particular pattern of oscillation. Then, the transformed well-established feature is measured for each PC in order to classify it into either speech or music based on the baseline classification system using a RF machine learning technique. The classification performance of real-world soundtracks is effectively improved, which is demonstrated by comparing speech/music recognition using conventional classification methods and the proposed SSA method. The second proposed and de-veloped method can detect pure speech, pure music, and mix with a much lower complexity level

Cyclic Boronates Inhibit All Classes of β-Lactamase

β-Lactamase-mediated resistance is a growing threat to the continued use of β-lactam antibiotics. The use of the β-lactam-based serine-β-lactamase (SBL) inhibitors clavulanic acid, sulbactam, tazobactam, and, more recently, the non-β-lactam inhibitor avibactam has extended the utility of β-lactams against bacterial infections demonstrating resistance via these enzymes. These molecules are, however, ineffective against the metallo-β-lactamases (MBLs), which catalyse their hydrolysis. To date, there are no clinically available metallo-β-lactamase inhibitors. Co-production of MBLs and SBLs in resistant infections is, thus, of major clinical concern. The development of ‘dual-action' inhibitors, targeting both SBLs and MBLs, is of interest, but these are considered difficult to achieve due to the structural and mechanistic differences between the two enzyme classes. We recently reported evidence that cyclic boronates can inhibit both serine- and metallo-β-lactmases. Here we report that cyclic boronates are able to inhibit all four classes of β-lactamase, including the class A extended spectrum β-lactamase, CTX-M-15, the class C enzyme, AmpC from Pseudomonas aeruginosa, and class D OXA enzymes with carbapenem-hydrolysing capabilities. We demonstrate that cyclic boronates can potentiate the use of β-lactams against Gram-negative clinical isolates expressing a variety of β-lactamases. Comparison of a crystal structure of a CTX-M-15:cyclic boronate complex with structures of cyclic boronates complexed with other β-lactamases reveals remarkable conservation of the small molecule binding mode, supporting our proposal that these molecules work by mimicking the common tetrahedral anionic intermediate present in both serine- and metallo-β-lactamase catalysis

Importance of Ethnicity, CYP2B6 and ABCB1 Genotype for Efavirenz Pharmacokinetics and Treatment Outcomes: A Parallel-group Prospective Cohort Study in two sub-Saharan Africa Populations.

We evaluated the importance of ethnicity and pharmacogenetic variations in determining efavirenz pharmacokinetics, auto-induction and immunological outcomes in two African populations. ART naïve HIV patients from Ethiopia (n = 285) and Tanzania (n = 209) were prospectively enrolled in parallel to start efavirenz based HAART. CD4+ cell counts were determined at baseline, 12, 24 and 48 weeks. Plasma and intracellular efavirenz and 8-hydroxyefvairenz concentrations were determined at week 4 and 16. Genotyping for common functional CYP2B6, CYP3A5, ABCB1, UGT2B7 and SLCO1B1 variant alleles were done. Patient country, CYP2B6*6 and ABCB1 c.4036A>G (rs3842A>G) genotype were significant predictors of plasma and intracellular efavirenz concentration. CYP2B6*6 and ABCB1 c.4036A>G (rs3842) genotype were significantly associated with higher plasma efavirenz concentration and their allele frequencies were significantly higher in Tanzanians than Ethiopians. Tanzanians displayed significantly higher efavirenz plasma concentration at week 4 (p<0.0002) and week 16 (p = 0.006) compared to Ethiopians. Efavirenz plasma concentrations remained significantly higher in Tanzanians even after controlling for the effect of CYP2B6*6 and ABCB1 c.4036A>G genotype. Within country analyses indicated a significant decrease in the mean plasma efavirenz concentration by week 16 compared to week 4 in Tanzanians (p = 0.006), whereas no significant differences in plasma concentration over time was observed in Ethiopians (p = 0.84). Intracellular efavirenz concentration and patient country were significant predictors of CD4 gain during HAART. We report substantial differences in efavirenz pharmacokinetics, extent of auto-induction and immunologic recovery between Ethiopian and Tanzanian HIV patients, partly but not solely, due to pharmacogenetic variations. The observed inter-ethnic variations in efavirenz plasma exposure may possibly result in varying clinical treatment outcome or adverse event profiles between populations

The COVID-19 pandemic and healthcare systems in Africa: a scoping review of preparedness, impact and response.

BACKGROUND: The COVID-19 pandemic has overwhelmed health systems in both developed and developing nations alike. Africa has one of the weakest health systems globally, but there is limited evidence on how the region is prepared for, impacted by and responded to the pandemic. METHODS: We conducted a scoping review of PubMed, Scopus, CINAHL to search peer-reviewed articles and Google, Google Scholar and preprint sites for grey literature. The scoping review captured studies on either preparedness or impacts or responses associated with COVID-19 or covering one or more of the three topics and guided by Arksey and O'Malley's methodological framework. The extracted information was documented following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension checklist for scoping reviews. Finally, the resulting data were thematically analysed. RESULTS: Twenty-two eligible studies, of which 6 reported on health system preparedness, 19 described the impacts of COVID-19 on access to general and essential health services and 7 focused on responses taken by the healthcare systems were included. The main setbacks in health system preparation included lack of available health services needed for the pandemic, inadequate resources and equipment, and limited testing ability and surge capacity for COVID-19. Reduced flow of patients and missing scheduled appointments were among the most common impacts of the COVID-19 pandemic. Health system responses identified in this review included the availability of telephone consultations, re-purposing of available services and establishment of isolation centres, and provisions of COVID-19 guidelines in some settings. CONCLUSIONS: The health systems in Africa were inadequately prepared for the pandemic, and its impact was substantial. Responses were slow and did not match the magnitude of the problem. Interventions that will improve and strengthen health system resilience and financing through local, national and global engagement should be prioritised

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

PARP14 promotes the warburg effect in hepatocellular carcinoma by inhibiting JNK1-dependent PKM2 phosphorylation and activation

Most tumour cells use aerobic glycolysis (the Warburg effect) to support anabolic growth and evade apoptosis. Intriguingly, the molecular mechanisms that link the Warburg effect with the suppression of apoptosis are not well understood. In this study, using loss-of-function studies in vitro and in vivo, we show that the anti-apoptotic protein poly(ADP-ribose) polymerase (PARP)14 promotes aerobic glycolysis in human hepatocellular carcinoma (HCC) by maintaining low activity of the pyruvate kinase M2 isoform (PKM2), a key regulator of the Warburg effect. Notably, PARP14 is highly expressed in HCC primary tumours and associated with poor patient prognosis. Mechanistically, PARP14 inhibits the pro-apoptotic kinase JNK1, which results in the activation of PKM2 through phosphorylation of Thr365. Moreover, targeting PARP14 enhances the sensitization of HCC cells to anti-HCC agents. Our findings indicate that the PARP14-JNK1-PKM2 regulatory axis is an important determinant for the Warburg effect in tumour cells and provide a mechanistic link between apoptosis and metabolism

Antiproliferative effect of Tualang honey on oral squamous cell carcinoma and osteosarcoma cell lines

<p>Abstract</p> <p>Background</p> <p>The treatment of oral squamous cell carcinomas (OSCC) and human osteosarcoma (HOS) includes surgery and/or radiotherapy which often lead to reduced quality of life. This study was aimed to study the antiproliferative activity of local honey (Tualang) on OSCC and HOS cell lines.</p> <p>Methods</p> <p>Several concentrations of Tualang honey (1% - 20%) were applied on OSCC and HOS cell lines for 3, 6, 12, 24, 48 and 72 hours. Morphological characteristics were observed under light and fluorescent microscope. Cell viability was assessed using MTT assay and the optical density for absorbance values in each experiment was measured at 570 nm by an ELISA reader. Detection of cellular apoptosis was done using the Annexin V-FITC Apoptosis Detection Kit.</p> <p>Results</p> <p>Morphological appearance showed apoptotic cellular changes like becoming rounded, reduction in cell number, blebbed membrane and apoptotic nuclear changes like nuclear shrinkage, chromatin condensation and fragmented nucleus on OSCC and HOS cell lines. Cell viability assay showed a time and dose-dependent inhibitory effect of honey on both cell lines. The 50% inhibitory concentration (IC_<b>50</b>) for OSCC and HOS cell lines was found to be 4% and 3.5% respectively. The maximum inhibition of cell growth of ≥80% was obtained at 15% for both cell lines. Early apoptosis was evident by flow cytometry where percentage of early apoptotic cells increased in dose and time dependent manner.</p> <p>Conclusion</p> <p>Tualang honey showed antiproliferative effect on OSCC and HOS cell lines by inducing early apoptosis.</p