Extant Sequence Reconstruction: The Accuracy of Ancestral Sequence Reconstructions Evaluated by Extant Sequence Cross-Validation.

Ancestral sequence reconstruction (ASR) is a phylogenetic method widely used to analyze the properties of ancient biomolecules and to elucidate mechanisms of molecular evolution. Despite its increasingly widespread application, the accuracy of ASR is currently unknown, as it is generally impossible to compare resurrected proteins to the true ancestors. Which evolutionary models are best for ASR? How accurate are the resulting inferences? Here we answer these questions using a cross-validation method to reconstruct each extant sequence in an alignment with ASR methodology, a method we term "extant sequence reconstruction" (ESR). We thus can evaluate the accuracy of ASR methodology by comparing ESR reconstructions to the corresponding known true sequences. We find that a common measure of the quality of a reconstructed sequence, the average probability, is indeed a good estimate of the fraction of correct amino acids when the evolutionary model is accurate or overparameterized. However, the average probability is a poor measure for comparing reconstructions from different models, because, surprisingly, a more accurate phylogenetic model often results in reconstructions with lower probability. While better (more predictive) models may produce reconstructions with lower sequence identity to the true sequences, better models nevertheless produce reconstructions that are more biophysically similar to true ancestors. In addition, we find that a large fraction of sequences sampled from the reconstruction distribution may have fewer errors than the single most probable (SMP) sequence reconstruction, despite the fact that the SMP has the lowest expected error of all possible sequences. Our results emphasize the importance of model selection for ASR and the usefulness of sampling sequence reconstructions for analyzing ancestral protein properties. ESR is a powerful method for validating the evolutionary models used for ASR and can be applied in practice to any phylogenetic analysis of real biological sequences. Most significantly, ESR uses ASR methodology to provide a general method by which the biophysical properties of resurrected proteins can be compared to the properties of the true protein.

Evaluation of analyte-specific reagents for the direct detection of Pneumocystis jirovecii.

Pneumocystis jirovecii pneumonia (PJP) is a serious and sometimes fatal infection occurring in immunocompromised individuals. High-risk patients include those with low CD4 counts due to human immunodeficiency virus infection and transplant recipients. The incidence of PJP is increasing, and rapid detection of PJP is needed to effectively target treatment and improve patient outcomes. A common method used is an immunofluorescent assay (IFA), which has limitations, including labor costs, low sensitivity, and requirement for expert interpretation. This study evaluates the performance of the DiaSorin Molecular Pneumocystis jirovecii analyte-specific reagent (ASR) in a laboratory-developed test (LDT) for the direct detection of P. jirovecii DNA without prior nucleic acid extraction. Respiratory samples (n = 135) previously tested by IFA from 111 patients were included. Using a composite standard of in-house IFA and reference lab PJP PCR, the percent positive agreement for the LDT using the DiaSorin ASR was 97.8% (90/92). The negative percent agreement was 97.7% (42/43). The lower limit of detection of the assay was determined to be 1,200 copies/mL in bronchoalveolar lavage fluid. Analytical specificity was assessed using cultures of oropharyngeal flora and common respiratory bacterial and fungal pathogens. No cross-reactivity was observed. Our study suggests that the DiaSorin Pneumocystis ASR accurately detects P. jirovecii DNA and demonstrates improved sensitivity compared to the IFA method. IMPORTANCE: Our study is unique compared to other previously published studies on the DiaSorin analyte-specific reagent (ASR) because we focused on microbiological diagnostic methods commonly used (immunofluorescent assay) as opposed to pathology findings or reference PCR. In addition, in our materials and methods, we describe the protocol for the use of the DiaSorin ASR as a singleplex assay, which will allow other users to evaluate the ASR for clinical use in their lab.

Angiosperm flowers reached their highest morphological diversity early in their evolutionary history.

Flowers are the complex and highly diverse reproductive structures of angiosperms. Because of their role in sexual reproduction, the evolution of flowers is tightly linked to angiosperm speciation and diversification. Accordingly, the quantification of floral morphological diversity (disparity) among angiosperm subgroups and through time may give important insights into the evolutionary history of angiosperms as a whole. Based on a comprehensive dataset focusing on 30 characters describing floral structure across angiosperms, we used 1201 extant and 121 fossil flowers to measure floral disparity and explore patterns of floral evolution through time and across lineages. We found that angiosperms reached their highest floral disparity in the Early Cretaceous. However, decreasing disparity toward the present likely has not precluded the innovation of other complex traits at other morphological levels, which likely played a key role in the outstanding angiosperm species richness. Angiosperms occupy specific regions of the theoretical morphospace, indicating that only a portion of the possible floral trait combinations is observed in nature. The ANA grade, the magnoliids, and the early-eudicot grade occupy large areas of the morphospace (higher disparity), whereas nested groups occupy narrower regions (lower disparity).

The correlations on psychopathology in children self-rating, psychopathology in children as related by their parents and psychopathology in parents self-rating in a Kenyan school setting: towards an inclusive family-centered approach.

Several studies have reported on the association between parental and childhood psychopathologies. Despite this, little is known about the psychopathologies between parents and children in a non-clinical population. We present such a study, the first in a Kenyan setting in an attempt to fill this gap. The objective of this study was to determine the association between self-rating psychopathology in children, parent-rating psychopathology in their children and self-rating psychopathology in parents in a non-clinical population of children attending schools in Kenya. We identified 113 participants, comprising children and their parents in 10 randomly sampled primary schools in South East Kenya. The children completed the Youth Self-Report (YSR) scale and parents completed the Child Behavior Check List (CBCL) on their children and the Adult Self-Reports (ASR) on themselves. These instruments are part of the Achenbach System of Empirically Based Assessment (ASEBA), developed in the USA for a comprehensive approach to assessing adaptation and maladaptive behavior in children and adolescents. There was back and forth translation of the instruments from English to Swahili and the local dialect, Kamba. Every revision of the English translation was sent to the instrument author who sent back comments until the revised version was in sync with the version developed by the author. We used the ASEBA in-built algorithm for scoring to determine cut-off points for problematic and non-problematic behavior. Correlations, linear regression and independent sample t-test were used to explore these associations. The mean age of the children was 12.7. While there was no significant association between child problems as measured by YSR (self-reported) and parent problems as measured by ASR and CBCL in the overall correlations, there was a significant association when examining specific groups (clinical range vs. non-clinical). Moreover, significant association existed between total problems on YSR and ASR internalizing problems (t=-2.3,p = 0.023), with clinical range having a higher mean than the normal range. In addition, a significant relationship (p < 0.05) was found between psychopathology in children as reported by both parents (CBCL) and psychopathology in parents as self-reported (ASR).Mothers were more likely to report lower syndrome scores of their children as compared to fathers. Our findings indicate discrepancies between children self-rating and parent ratings, suggesting that one cannot manage psychopathology in children without reference to psychopathology in their parents. We suggest broad-based psycho-education to include children and parents to enhance shared awareness of psychopathology and uptake of treatment.

Development History, Structure, and Function of ASR (Abscisic Acid-Stress-Ripening) Transcription Factor.

Abiotic and biotic stress factors seriously affect plant growth and development. The process of plant response to abiotic stress involves the synergistic action of multiple resistance genes. The ASR (Abscisic acid stress-ripening) gene is a plant-specific transcription factor that plays a central role in regulating plant senescence, fruit ripening, and response to abiotic stress. ASR family members are highly conserved in plant evolution and contain ABA/WBS domains. ASR was first identified and characterized in tomatoes (Solanum lycopersicum L.). Subsequently, the ASR gene has been reported in many plant species, extending from gymnosperms to monocots and dicots, but lacks orthologues in Arabidopsis (Arabidopsis thaliana). The promoter regions of ASR genes in most species contain light-responsive elements, phytohormone-responsive elements, and abiotic stress-responsive elements. In addition, ASR genes can respond to biotic stresses via regulating the expression of defense genes in various plants. This review comprehensively summarizes the evolutionary history, gene and protein structures, and functions of the ASR gene family members in plant responses to salt stress, low temperature stress, pathogen stress, drought stress, and metal ions, which will provide valuable references for breeding high-yielding and stress-resistant plant varieties.

Modeling the zinc effect on OsASR5-STAR1 promoter interaction by molecular dynamics.

Intrinsically disordered proteins (IDPs) have numerous dynamic conformations. Given the difficulties in tracking temporarily folded states of this kind of protein, methods such as molecular modeling and molecular dynamics (MD) simulations make the process less costly, less laborious, and more detailed. Few plant IDPs have been characterized so far, such as proteins from the Abscisic acid, Stress and Ripening (ASR) family. The present work applied, for the first time, the two above-mentioned tools to test the feasibility of determining a three-dimensional transition model of OsASR5 and to investigate the relationship between OsASR5 and zinc. We found that one of OsASR5's conformers contains α-helices, turns, and loops and that the metal binding resulted in a predominance of α-helix. This stability is possibly imperative for the transcription factor activity. The promoter region of a sugar transporter was chosen to test this hypothesis and free energy calculations showed how the ion is mandatory for this complex formation. The results produced here aim to clarify which conformation the protein in the bound state assumes and which residues are involved in the process, besides developing the understanding of how the flexibility of these proteins can contribute to the response to environmental stresses.

The Global Burden of Liver Disease.

Chronic liver disease (CLD) and its associated complications (cirrhosis and liver cancer) cause significant mortality, morbidity, and economic burden. Published data from the World Health Organization and/or the Global Burden of Disease show that the burden of CLD is large and increasing, primarily owing to the increasing burden of nonalcoholic fatty liver disease and alcohol-related liver disease (ALD). Middle Eastern, Northern African, and Asian regions of the globe are most affected by hepatitis B and hepatitis C virus. Furthermore, Middle Eastern and North African regions also are affected by nonalcoholic fatty liver disease, and Eastern European, West African, and Central Asian regions are affected by ALD. In this context, the rate of increase for cirrhosis is highest in the Middle East, as well as in middle high and high sociodemographic index (SDI) regions. On the other hand, the highest SDI countries are experiencing increasing rates of hepatocellular carcinoma (HCC). Assessing HCC burden based on country and etiology shows that China, Korea, India, Japan, and Thailand have the highest hepatitis B virus-related HCC cases, while China, Japan, and the United States have the highest hepatitis C virus-related HCC cases. Additionally, the United States has the highest ALD-related HCC cases, while India, the United States, and Thailand have the highest nonalcoholic steatohepatitis-related HCC cases. Although the burden of CLD is increasing globally, regions of the world are impacted differently as a result of a number of sociodemographic factors.

Resistance to Powdery Mildew Is Conferred by Different Genetic Loci at the Adult-Plant and Seedling Stages in Winter Wheat Line Tianmin 668.

Winter wheat line Tianmin 668 was crossed with susceptible cultivar Jingshuang 16 to develop 216 recombinant inbred lines (RILs) for dissecting its adult-plant resistance (APR) and all-stage resistance (ASR) against powdery mildew. The RIL population was genotyped on a 16K genotyping by target sequencing single-nucleotide polymorphism array and phenotyped in six field trials and in the greenhouse. Three loci-QPmtj.caas-2BL, QPmtj.caas-2AS, and QPmtj.caas-5AL-conferring APR to powdery mildew were detected on chromosomes 2BL, 2AS, and 5AL, respectively, of Tianmin 668. The effect of resistance to powdery mildew for QPmtj.caas-2BL was greater than that of the other two loci. A Kompetitive allele-specific PCR marker specific for QPmtj.caas-2BL was developed and verified on 402 wheat cultivars or breeding lines. Results of virulence and avirulence patterns to 17 Blumeria graminis f. sp. tritici isolates, bulked segregant analysis-RNA-sequencing, and a genetic linkage mapping identified a resistance allele at locus Pm4 in Tianmin 668 based on the seedling phenotypes of the RIL population. The PCR-based DNA sequence alignment and cosegregation of the functional marker with the phenotypes of the RIL population demonstrated that Pm4d was responsible for the ASR to isolate Bgt1 in Tianmin 668. The dissection of genetic loci for APR and ASR may facilitate the application of Tianmin 668 in developing powdery mildew-resistant wheat cultivars.

Identification of the Abscisic Acid-, Stress-, and Ripening-Induced (ASR) Family Involved in the Adaptation of Tetragonia tetragonoides (Pall.) Kuntze to Saline-Alkaline and Drought Habitats.

Tetragonia tetragonoides (Pall.) Kuntze (Aizoaceae, 2n = 2x = 32), a vegetable used for both food and medicine, is a halophyte that is widely distributed in the coastal areas of the tropics and subtropics. Saline-alkaline soils and drought stress are two major abiotic stressors that significantly affect the distribution of tropical coastal plants. Abscisic acid-, stress-, and ripening-induced (ASR) proteins belong to a family of plant-specific, small, and hydrophilic proteins with important roles in plant development, growth, and abiotic stress responses. Here, we characterized the ASR gene family from T. tetragonoides, which contained 13 paralogous genes, and divided TtASRs into two subfamilies based on the phylogenetic tree. The TtASR genes were located on two chromosomes, and segmental duplication events were illustrated as the main duplication method. Additionally, the expression levels of TtASRs were induced by multiple abiotic stressors, indicating that this gene family could participate widely in the response to stress. Furthermore, several TtASR genes were cloned and functionally identified using a yeast expression system. Our results indicate that TtASRs play important roles in T. tetragonoides' responses to saline-alkaline soils and drought stress. These findings not only increase our understanding of the role ASRs play in mediating halophyte adaptation to extreme environments but also improve our knowledge of plant ASR protein evolution.

Narrative recall in relapsing-remitting multiple sclerosis: A potentially useful speech task for detecting subtle cognitive changes.

Our research studied relapsing-remitting multiple sclerosis (RRMS). In half of the RRMS cases, mild cognitive difficulties are present, but often remain undetected despite their adverse effects on individuals' daily life. Detecting subtle cognitive alterations using speech analysis have rarely been implemented in MS research. We applied automatic speech recognition technology to devise a speech task with potential diagnostic value. Therefore, we used two narrative tasks adjusted for the neural and cognitive characteristics of RRMS; namely narrative recall and personal narrative. In addition to speech analysis, we examined the information processing speed, working memory, verbal fluency, and naming skills. Twenty-one participants with RRMS and 21 gender-, age-, and education-matched healthy controls took part in the study. All the participants with RRMS achieved a normal performance on Addenbrooke's Cognitive Examination. The following parameters of speech were measured: articulation and speech rate, the proportion, duration, frequency, and average length of silent and filled pauses. We found significant differences in the temporal parameters between groups and speech tasks. ROC analysis produced high classification accuracy for the narrative recall task (0.877 and 0.866), but low accuracy for the personal narrative task (0.617 and 0.592). The information processing speed affected the speech of the RRMS group but not that of the control group. The higher cognitive load of the narrative recall task may be the cause of significant changes in the speech of the RRMS group relative to the controls. Results suggest that narrative recall task may be effective for detecting subtle cognitive changes in RRMS.

Ancestral reconstruction of mammalian FMO1 enables structural determination, revealing unique features that explain its catalytic properties.

Mammals rely on the oxidative flavin-containing monooxygenases (FMOs) to detoxify numerous and potentially deleterious xenobiotics; this activity extends to many drugs, giving FMOs high pharmacological relevance. However, our knowledge regarding these membrane-bound enzymes has been greatly impeded by the lack of structural information. We anticipated that ancestral-sequence reconstruction could help us identify protein sequences that are more amenable to structural analysis. As such, we hereby reconstructed the mammalian ancestral protein sequences of both FMO1 and FMO4, denoted as ancestral flavin-containing monooxygenase (AncFMO)1 and AncFMO4, respectively. AncFMO1, sharing 89.5% sequence identity with human FMO1, was successfully expressed as a functional enzyme. It displayed typical FMO activities as demonstrated by oxygenating benzydamine, tamoxifen, and thioanisole, drug-related compounds known to be also accepted by human FMO1, and both NADH and NADPH cofactors could act as electron donors, a feature only described for the FMO1 paralogs. AncFMO1 crystallized as a dimer and was structurally resolved at 3.0 Å resolution. The structure harbors typical FMO aspects with the flavin adenine dinucleotide and NAD(P)H binding domains and a C-terminal transmembrane helix. Intriguingly, AncFMO1 also contains some unique features, including a significantly porous and exposed active site, and NADPH adopting a new conformation with the 2'-phosphate being pushed inside the NADP+ binding domain instead of being stretched out in the solvent. Overall, the ancestrally reconstructed mammalian AncFMO1 serves as the first structural model to corroborate and rationalize the catalytic properties of FMO1.

Worldwide Burden of, Risk Factors for, and Trends in Pancreatic Cancer.

BACKGROUND & AIMS: We evaluated global and regional burdens of, risk factors for, and epidemiologic trends in pancreatic cancer among groups of different sexes and ages. METHODS: We used data from the GLOBOCAN database to estimate pancreatic cancer incidence and mortality in 184 countries. We examined the association between lifestyle and metabolic risk factors, extracted from the World Health Organization Global Health Observatory database, and pancreatic cancer incidence and mortality by univariable and multivariable linear regression. We retrieved country-specific age-standardized rates (ASRs) of incidence and mortalities from cancer registries from 48 countries through 2017 for trend analysis by joinpoint regression analysis. RESULTS: The highest incidence and mortality of pancreatic cancer were in regions with very high (ASRs, 7.7 and 4.9) and high human development indexes (ASRs, 6.9 and 4.6) in 2018. Countries with higher incidence and mortality were more likely to have higher prevalence of smoking, alcohol drinking, physical inactivity, obesity, hypertension, and high cholesterol. From 2008 to 2017, 2007 to 2016, or 2003 to 2012, depending on the availability of the data, there were increases in incidence among men and women in 14 (average annual percent changes [AAPCs], 8.85 to 0.41) and 17 (AAPCs, 6.04 to 0.87) countries, respectively. For mortality, the increase was observed in 8 (AAPCs, 4.20 to 0.55) countries among men and 14 (AAPCs, 5.83 to 0.78) countries among women. Although the incidence increased in 18 countries (AAPCs, 7.83 to 0.91) among individuals 50 years or older, an increasing trend in pancreatic cancer was also identified among individuals younger than 50 years and 40 years in 8 (AAPCs, 8.75 to 2.82) and 4 (AAPCs, 11.07 to 8.31) countries, respectively. CONCLUSIONS: In an analysis of data from 48 countries, we found increasing incidence and mortality trends in pancreatic cancer, especially among women and populations 50 years or older, but also among younger individuals. More preventive efforts are recommended for these populations.

ThASR3 confers salt and osmotic stress tolerances in transgenic Tamarix and Arabidopsis.

BACKGROUND: ASR (abscisic acid-, stress-, and ripening-induced) gene family plays a crucial role in responding to abiotic stresses in plants. However, the roles of ASR genes protecting plants against high salt and drought stresses remain unknown in Tamarix hispida. RESULTS: In this study, a salt and drought-induced ASR gene, ThASR3, was isolated from Tamarix hispida. Transgenic Arabidopsis overexpressing ThASR3 exhibited stimulating root growth and increasing fresh weight compared with wild-type (WT) plants under both salt and water deficit stresses. To further analyze the gain- and loss-of-function of ThASR3, the transgenic T. hispida plants overexpressing or RNA interference (RNAi)-silencing ThASR3 were generated using transient transformation. The overexpression of ThASR3 in Tamarix and Arabidopsis plants displayed enhanced reactive oxygen species (ROS) scavenging capability under high salt and osmotic stress conditions, including increasing the activities of antioxidant enzymes and the contents of proline and betaine, and reducing malondialdehyde (MDA) content and electrolyte leakage rates. CONCLUSION: Our results indicate that ThASR3 functions as a positive regulator in Tamarix responses to salt and osmotic stresses and confers multiple abiotic stress tolerances in transgenic plants, which may have an important application value in the genetic improvement of forest tree resistance.

Genome-wide association study for resistance in bread wheat (Triticum aestivum L.) to stripe rust (Puccinia striiformis f. sp. tritici) races in Argentina.

BACKGROUND: Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is one of the most devastating diseases of the wheat crop. It causes significant reductions in both grain yield and grain quality. In recent years, new and more virulent races have overcome many of the known resistance genes in Argentinian germplasm. In order to identify loci conferring resistance to the local races of Pst for effective utilization in future breeding programs, a genome-wide association study (GWAS) was performed using a collection of 245 bread wheat lines genotyped with 90 K SNPs. RESULTS: To search for adult plant resistance (APR) the panel was evaluated for disease severity (DS) and area under disease progress curve (AUDPC) in field trials during two years under natural infection conditions. To look for seedling or all-stage resistance (ASR) the panel was evaluated to determine infection type (IT) under greenhouse conditions against two prevalent races in Argentina. The phenotypic data showed that the panel possessed enough genetic variability for searching for sources of resistance to Pst. Significant correlations between years were observed for Pst response in the field and high heritability values were found for DS (H2 = 0.89) and AUDPC (H2 = 0.93). Based on GWAS, eight markers associated with Pst resistance (FDR < 0.01) were identified, of these, five were associated with ASR (on chromosomes 1B, 2A, 3A and 5B) and three with APR (on chromosomes 3B and 7A). These markers explained between 2% and 32.62% of the phenotypic variation. Five of the markers corresponded with previously reported Yr genes/QTL, while the other three (QYr.Bce.1B.sd.1, QYr.Bce.3A.sd and QYr.Bce.3B.APR.2) might be novel resistance loci. CONCLUSION: Our results revealed high genetic variation for resistance to Argentinian stripe rust races in the germplasm used here. It constitutes a very promising step towards the improvement of Pst resistance of bread wheat in Argentina. Also, the identification of new resistance loci would represent a substantial advance for diversifying the current set of resistance genes and to advance in the improvement of the durable resistance to the disease.

A case study of distress mechanism(s) in a concrete structure foundation in the saturated zone and above the saturated zone.

In this case study, distress mechanism(s) of a concrete structure in the saturated and unsaturated zones of the foundation were investigated. This research was performed using a stereomicroscope, polarised light microscopy (PLM), and a limited study using a scanning electron microscope (SEM) with backscattered electron (BSE). Results of this study showed that concrete cores extracted from both the saturated and unsaturated zones of the foundation exhibited severe to moderate concrete distress, but the cause of the distress/cracking in the concrete was not related to Alkali-Carbonate Reaction (ACR) as was initially suspected. While the damage to the concrete extracted from the structure above the saturated zone of the foundation was caused by a combination of Alkali-Silica Reaction (ASR) and freeze-thaw deterioration, concrete distress in the saturated zone of the foundation was caused primarily by ASR of shale particles in the natural sand fine aggregate. The sand also contained traces of chert particles with ASR. Limited ASR was seen in the crushed gravel coarse aggregate siliceous limestone, dolomitic limestone, and chert particles. Results of this case study showed that siliceous shale particles in the fine aggregate caused detrimental ASR damage to the concrete, and thus caution needs to be exercised when aggregate containing shale is used in concrete.

Neonatal ventral hippocampus lesion disrupts maternal behavior in rats: An animal model of schizophrenia.

Although individuals with schizophrenia typically present deficits in social interaction, little is known about the quality of their parent-infant interactions. In the present study, we assessed the behavioral effects of neonatal ventral hippocampus lesion (nVHL) in female rats (nVHL is known to induce schizophrenia-like deficits in males). Sexually naïve adult nVHL or sham female rats received cognitive and social tests, and their maternal behavior was observed in independent groups of adult nVHL and sham rats on postpartum days 2, 6, and 12. Compared to Sham females, naïve nVHL rats displayed elevated locomotor activity, less social interaction, and disrupted habituation of the acoustic startle response (ASR), while dorsal immobility (a defensive behavioral response) and prepulse inhibition of ASR were not affected. Although all nVHL mothers retrieved their pups, adopted the crouching posture, and nursed them, they showed disturbances in the display of pup body licking and nest building. Furthermore, a high proportion of nVHL mothers displayed atypical retrieval of pups and re-retrieving of pups, atypical nest-building, excavation, and cannibalism, as well a high level of these behaviors. These data indicate that cognition, locomotor activity, and maternal care is disrupted in nVHL female, suggesting disturbances in mesocorticolimbic dopaminergic systems and/or in social cognition.

The global burden of nasopharyngeal carcinoma from 2009 to 2019: an observational study based on the Global Burden of Disease Study 2019.

PURPOSE: The incidence and mortality rate of nasopharyngeal carcinoma (NPC) has changed in recent years. Our goal is to determine the epidemiological pattern of NPC to help policymakers allocate limited medical resources. METHODS: Detailed information about NPC from 2009 to 2019 was collected from the Global Burden of Disease 2019 database. Age-standardized rates (ASRs) and corresponding estimated annual percentage changes (EAPCs) were calculated to assess NPC's incidence and mortality trends. RESULTS: Globally, there was a consistent increase in the NPC incidence cases from 2009 to 2019 (from 121.65 × 103 cases in 2009 to 176.50 × 103 cases in 2019, increasing by 45.09%). The age-standardized incidence rate (ASIR) of NPC increased from 1.81 in 2009 to 2.12 in 2019 (EAPC = 1.59, 95% CI 1.36-1.81). On the contrary, the mortality of NPC showed a downward trend (ASDR: 0.93 in 2009 and 0.86 in 2019; EAPC = - 0.63, 95% CI - 0.78 to - 0.48), and it was negatively correlated with the social demographic index (SDI) in most regions. Both incidence and mortality rates of high-incidence territories tended to be stable or decline. Males had significantly higher incidence and mortality of NPC than females. The number of patients with onset age greater than 50 years old accounted for the highest proportion. We found that smoking, occupational exposure to formaldehyde, and alcohol use were the main risk factors for NPC-related mortality. CONCLUSION: Globally, the incidence rate of NPC has been slightly increasing, while the mortality and disability-adjusted life years (DALYs) have been decreasing. NPC burden in high-middle and middle SDI areas was the heaviest. The current prevention strategy should be repositioned, and some countries should formulate more targeted approaches to reduce the current burden of NPC.

Domain Adaptation with Augmented Data by Deep Neural Network Based Method Using Re-Recorded Speech for Automatic Speech Recognition in Real Environment.

The most effective automatic speech recognition (ASR) approaches are based on artificial neural networks (ANN). ANNs need to be trained with an adequate amount of matched conditioned data. Therefore, performing training adaptation of an ASR model using augmented data of matched condition as the real environment gives better results for real data. Real-world speech recordings can vary in different acoustic aspects depending on the recording channels and environment such as the Long Term Evolution (LTE) channel of mobile telephones, where data are transmitted with voice over LTE (VoLTE) technology, wireless pin mics in a classroom condition, etc. Acquiring data with such variation is costly. Therefore, we propose training ASR models with simulated augmented data and fine-tune them for domain adaptation using deep neural network (DNN)-based simulated data along with re-recorded data. DNN-based feature transformation creates realistic speech features from recordings of clean conditions. In this research, a comparative investigation is performed for different recording channel adaptation methods for real-world speech recognition. The proposed method yields 27.0% character error rate reduction (CERR) for the DNN-hidden Markov model (DNN-HMM) hybrid ASR approach and 36.4% CERR for the end-to-end ASR approach for the target domain of the LTE channel of telephone speech.

Using Automatic Speech Recognition to Assess Thai Speech Language Fluency in the Montreal Cognitive Assessment (MoCA).

The Montreal cognitive assessment (MoCA), a widely accepted screening tool for identifying patients with mild cognitive impairment (MCI), includes a language fluency test of verbal functioning; its scores are based on the number of unique correct words produced by the test taker. However, it is possible that unique words may be counted differently for various languages. This study focuses on Thai as a language that differs from English in terms of word combinations. We applied various automatic speech recognition (ASR) techniques to develop an assisted scoring system for the MoCA language fluency test with Thai language support. This was a challenge because Thai is a low-resource language for which domain-specific data are not publicly available, especially speech data from patients with MCIs. Furthermore, the great variety of pronunciation, intonation, tone, and accent of the patients, all of which might differ from healthy controls, bring more complexity to the model. We propose a hybrid time delay neural network hidden Markov model (TDNN-HMM) architecture for acoustic model training to create our ASR system that is robust to environmental noise and to the variation of voice quality impacted by MCI. The LOTUS Thai speech corpus was incorporated into the training set to improve the model's generalization. A preprocessing algorithm was implemented to reduce the background noise and improve the overall data quality before feeding data into the TDNN-HMM system for automatic word detection and language fluency score calculation. The results show that the TDNN-HMM model in combination with data augmentation using lattice-free maximum mutual information (LF-MMI) objective function provides a word error rate (WER) of 30.77%. To our knowledge, this is the first study to develop an ASR with Thai language support to automate the scoring system of MoCA's language fluency assessment.

Automatic Speech Recognition Performance Improvement for Mandarin Based on Optimizing Gain Control Strategy.

Automatic speech recognition (ASR) is an essential technique of human-computer interactions; gain control is a commonly used operation in ASR. However, inappropriate gain control strategies can lead to an increase in the word error rate (WER) of ASR. As there is a current lack of sufficient theoretical analyses and proof of the relationship between gain control and WER, various unconstrained gain control strategies have been adopted on realistic ASR systems, and the optimal gain control with respect to the lowest WER, is rarely achieved. A gain control strategy named maximized original signal transmission (MOST) is proposed in this study to minimize the adverse impact of gain control on ASR systems. First, by modeling the gain control strategy, the quantitative relationship between the gain control strategy and the ASR performance was established using the noise figure index. Second, through an analysis of the quantitative relationship, an optimal MOST gain control strategy with minimal performance degradation was theoretically deduced. Finally, comprehensive comparative experiments on a Mandarin dataset show that the proposed MOST gain control strategy can significantly reduce the WER of the experimental ASR system, with a 10% mean absolute WER reduction at -9 dB gain.