The involvement of decomposition and composition processes in restructuring during problem solving.

Decomposition of chunks has been widely accepted as a critical proxy of restructuring, but the role of composition in forming new representations has been largely neglected. This study aims to investigate the roles of both decomposition and composition processes in chunk restructuring, as well as their relationships with "aha" experiences during problem-solving. Participants were asked to move a part of a character to another character to create two new characters. Across three experiments, the characters to be decomposed or composed were varied in terms of tight or loose chunks. The results showed that decomposition or composition of tight chunks led to lower success rates, longer response times, and significantly stronger "Aha!" emotional experiences (mainly in terms of surprise and suddenness). This study provides evidence for the contribution of both decomposition and composition processes to restructuring in creative insight.

Micro-Red Blood Cell, Fragmented Red Blood Cell, Platelet Distribution Width, Mean Platelet Volume, and Platelet-Large Cell Ratio on Sysmex XN Series Hematology Analyzers Can Be Used for the Reflex Test of Impedance Platelet Count in Clinical Practice.

CONTEXT.­: Platelet (PLT) counting with impedance (PLT-I) is widely used but has low specificity. PLT counting with fluorescence (PLT-F), tested by the Sysmex XN series with high specificity, can be a complementary method to PLT-I. OBJECTIVE.­: To identify red blood cell (RBC)- and PLT-related parameters as potential influencing factors for PLT-I and establish PLT reflex test rules with PLT-F. DESIGN.­: We prospectively tested both PLT-I and PLT-F in all 3480 samples. In a development data set of 3000 samples, differences between the reflex and nonreflex groups were compared and influencing factors for PLT-I were identified by logistic regression. The area under the receiver operating characteristic (ROC) curve and cutoff values were obtained by ROC curve analysis. Validation was conducted in the remaining 480 samples (validation data set). RESULTS.­: PLT-F showed comparable results with immunoplatelet counting. In logistic regression, increased micro-RBC absolute count (micro-RBC#), fragmented RBC absolute count (FRC#), PLT distribution width (PDW), mean PLT volume (MPV), PLT-large cell ratio (P-LCR), and immature PLT fraction absolute count (IPF#) were influencing factors for PLT-I. In ROC curve analysis, the cutoff values of micro-RBC#, FRC#, PDW, MPV, and P-LCR were 0.64 × 106/µL, 0.082 × 106/µL, 15.40 fL, 11.15 fL, and 33.95%, respectively. The areas under the ROC curve of micro-RBC# and FRC# were 0.77 and 0.79, respectively. CONCLUSIONS.­: Micro-RBC#, FRC#, PDW, MPV, P-LCR, and IPF# were factors affecting PLT-I. Among them, micro-RBC# and FRC# were the most impactful factors. From our study results, micro-RBC#, FRC#, MPV, PDW, and P-LCR can be used to establish reflex test rules for PLT counting in clinical work.

IL12B and IL17 genes polymorphisms associated with differential susceptibility to juvenile idiopathic arthritis and juvenile-onset systemic lupus erythematosus in Chinese children.

Genetic factors play a crucial role in the immune response of juvenile idiopathic arthritis (JIA) and juvenile-onset systemic lupus erythematosus (JSLE). This study aimed to investigate the association of IL12B (rs3212227, rs6887695) and IL17 (rs2275913, rs763780) gene polymorphisms with the susceptibility of JIA and JSLE in Chinese children. A total of 303 healthy controls and 304 patients including 160 JIA and 144 patients were analyzed, and the genetic polymorphisms were genotyped by using a Sequenom MassArray system. There was a significant association between the IL12B rs3212227 genotype and the increased risk of JSLE (P = .01). For rs6887695, the minor allele C was significantly associated with the increased risk of JIA (odds ratio = 1.48, 95% confidence interval [CI] = 1.12-1.95, P = .005). Moreover, rs6887695 genotype was significantly associated with both JIA and JSLE susceptibility (P < .05). Besides, IL12B haplotype GC significantly associated with the increased risk of JIA (P = .016). However, no significant difference was found between the IL17 (rs2275913, rs763780) gene polymorphisms and JIA or JSLE susceptibility (P > .05). And similar genotype distributions of IL12B and IL17 polymorphisms were found between the patients with nephritis and without nephritis in JSLE (P > .05). Our results indicated that IL12B polymorphisms was associated with an increased risk for the development of JIA and JSLE in Chinese children, highlighting the involvement of inflammation in the pathogenesis of JIA and JSLE. Moreover, there was a risk haplotype in IL12B which could increase the risk of JIA.

Retrospective analysis of 77 pathologically confirmed cases of pulmonary mycosis in a hospital in the south Sichuan Basin, 2014-2021 / 中国热带医学

@#Abstract: Objective To observe the etiological distribution, basic information, clinical characteristics, imaging and pathological features, treatment regimens, and prognosis of pathologically confirmed cases of pulmonary mycosis, aiming to improve the diagnosis and treatment level of pulmonary mycosis. Methods The clinical, imaging and pathological data of patients with pulmonary mycosis diagnosed by pathological biopsy in the Affiliated Hospital of Southwest Medical University from January 2014 to December 2021 were retrospectively analyzed. Results There were 77 cases of pulmonary mycosis who were diagnosed by pathology, and of these patients, 42 cases (54.54%) suffered from pulmonary aspergillosis, 34 cases (44.16%) suffered from pulmonary cryptococcosis, and 1 case (1.30%) suffered from pulmonary mucormycosis. Among the 77 patients, there were 38 male and 39 female patients, with an age range of 25 to 68 years old (mean age 51.13±10.32 years old). The common respiratory symptoms on admission included cough (33 cases, 42.86%), hemoptysis (24 cases, 31.17%), expectoration (22 cases, 28.57%) and chest pain (13 cases, 16.88%). Chest imaging features mainly included pulmonary nodules (37 cases, 48.05%), cavity (14 cases, 18.18%) and air crescent sign (10 cases, 12.99%). In this study, the main treatment measures for pulmonary mycosis were surgical resection (47 cases, 61.04%) and antifungal therapy combined with surgical resection (19 cases, 24.68%). After active treatments, most of these patients (72/77, 93.51%) discharged with better condition. Conclusions Pulmonary aspergillosis and pulmonary cryptococcosis are common pulmonary mycosis diagnosed by pathology. The main respiratory symptoms on admission are cough, expectoration and hemoptysis. Pulmonary nodules are the most common imaging features, and "air crescent sign" can be seen in some patients with pulmonary aspergillosis. Most pulmonary mycosis can have good treatment outcomes. Combining fungal histopathological characteristics and fungal special staining such as Periodic Acid-Schiff (PAS) staining and Gomori methenamine silver (GMS) staining can identify most pathogenic fungi into genera, which has important clinical significance for the timely diagnosis and treatment of pulmonary mycosis

Gene editing of Duchenne muscular dystrophy using biomineralization-based spCas9 variant nanoparticles.

The CRISPR/Cas9 mediated genome editing have provided a promising strategy to correct multiple mutations of Duchenne muscular dystrophy (DMD). However, the delivery of CRISPR/Cas9 system into mammalian cell for DMD gene editing mainly relies on adeno associated virus (AAV)-mediated transport. Meanwhile, the protospacer adjacent motif (PAM) requirement of wild-typed Cas9 protein causing the target sites for exon splice acceptor site are restricted to limited regions. Here, we developed a biomineralized PAMLess Cas9 (SpRY) variant nanoparticles (Bm-SpRY NPs) for DMD gene editing in vitro and in vivo. This method described a facile synthesis of biomineralized NPs with high SpRY pDNA encapsulation efficiency. In vitro results show that the Bm-SpRY NPs have the obvious advantages of well biocompatibility and protecting SpRY pDNA from enzyme degradation and efficient delivery under high serum condition. Cell studies demonstrated that Bm-SpRY NPs enable rapid cellular uptake, endo-lysosomes escape and nucleus transport. Meanwhiles, the DMD gene editing via Bm-SpRY NPs pathway is transient process without genomic integration. We evaluated multiple target regions with different PAMs for the DMD exon 51 splice acceptor site through Bm-SpRY NPs method and found that the target region with TAG PAM has the highest editing efficiency and significant preferential mutation. In vivo results show that intramuscular injection of Bm-SpRY NPs enable DMD gene mutation in muscle tissue without tissue damage. This study may extend the advanced application of CRISPR system for DMD therapy. STATEMENT OF SIGNIFICANCE: The gene editing technology of CRISPR/Cas9 provides an effective treatment strategy for the Duchenne muscular dystrophy (DMD) therapy. However, the delivery of CRISPR system in mammalian cell mainly relies on viral mediated transport and the NGG or NAG requirement of wild-typed Cas9 protein limits the target region in DMD gene. Here, the present study provides a biomineralized PAM Less Cas9 (SpRY) variant nanoparticles (Bm-SpRY NPs) for DMD gene editing in vitro and in vivo. This study may extend the application of CRISPR system for DMD gene therapy.

Emergence of a Hypervirulent Tigecycline-Resistant Klebsiella pneumoniae Strain Co-producing bla NDM-1 and bla KPC-2 With an Uncommon Sequence Type ST464 in Southwestern China.

Emergence of bla NDM-1 and bla KPC-2 co-producing Klebsiella pneumoniae strains is currently attracting widespread attention, but little information is available about their tigecycline resistance, virulence, and prevalence in Southwest China. In July 2021, an extensively drug-resistant K. pneumoniae strain AHSWKP25 whose genome contained both bla NDM-1 and bla KPC-2 genes was isolated from the blood of a patient with the malignant hematological disease in Luzhou, China. We investigated the resistance profiles of AHSWKP25 using microbroth dilution, agar dilution, modified carbapenemase inactivation (mCIM), and EDTA-modified carbapenemase inactivation methods (eCIM). The virulence of AHSWKP25 was assessed through string tests, serum killing assays, and a Galleria mellonella larval infection model. Conjugation and plasmid stability experiments were conducted to determine the horizontal transfer capacity of plasmids. And efflux pump phenotype test and real-time quantitative reverse transcription-PCR (RT-PCR) were used to determine its efflux pump activity. Sequencing of AHSWKP25 determined that AHSWKP25 belonged to ST464, which is resistant to antibiotics such as carbapenems, tetracycline, fluoroquinolones, tigecycline, and fosfomycin. The efflux pump phenotype tests and RT-PCR results demonstrated that efflux pumps were overexpressed in the AHSWKP25, which promoted the tigecycline resistance of the bacteria. AHSWKP25 also showed hypervirulence and serum resistance in vitro model. AHSWKP25 carried several different plasmids that contained bla NDM-1, bla KPC-2, and mutated tet(A) genes. Sequence alignment revealed that the plasmids carrying bla NDM-1 and bla KPC-2 underwent recombination and insertion events, respectively. We demonstrated that an X3 plasmid carrying bla NDM-1 was transferred from pSW25NDM1 to E. coli J53. We also identified missense mutations in the ramR, rcsA, lon, and csrD genes of AHSWKP25. Our results highlighted the potential of bla NDM-1 and bla KPC-2 co-producing K. pneumoniae strains to further develop antimicrobial resistance and hypervirulent phenotypes, but measures should be taken to closely monitor and control the spread of superbugs with multidrug-resistant phenotypes and hypervirulence.

Genomic and Phenotypic Characterization of a Colistin-Resistant Escherichia coli Isolate Co-Harboring bla NDM-5, bla OXA-1, and bla CTX-M-55 Isolated from Urine.

Background: Colistin is one of the few options for treating carbapenem-resistant Enterobacterales (CREs). There is little available information about the epidemic status of colistin-resistant CREs in Southern Sichuan, China. This study mainly investigated the genomic and phenotypic characteristics of an extensively drug resistant E. coli LZ00114 isolated from Luzhou, China. Materials and Methods: In 2020, LZ00114 was isolated from the urine of a patient with hydronephrosis and urinary tract infection in Luzhou, China. We assessed the resistance profile of LZ00114 in the presence and absence of the protonophore carbonyl cyano-m-chlorophenylhydrazine (CCCP) and 1-(1-naphthylmethyl)-piperazine (NMP) by antimicrobial susceptibility testing. The growth kinetics, motility, and pathogenicity of LZ00114 were determined to evaluate its microbial characteristics. In combination with whole genome sequencing (WGS) and real-time reverse transcription PCR (RT-PCR), we comprehensively analyzed the resistance mechanisms of LZ00114. Results: LZ00114 was resistant to various antimicrobial agents, including meropenem, tetracycline, ciprofloxacin, gentamicin, fosfomycin, and polymyxin B. Notably, CCCP reversed the resistance of LZ00114 to polymyxin B. LZ00114 displayed high pathogenicity in the infection model (P<0.01) compared with the Lab-WT strain, and its growth rate and motility were not significantly different from the Lab-WT strain. WGS and conjugation revealed that LZ00114 belonged to ST410 and carried a bla NDM-5-harboring self-transmissible IncX3 plasmid and a multi-replicon IncFII/FIA/FIB plasmid carrying bla OXA-1-bla CTX-M-55-tet(B)-aac(6')-Ib-cr-dfrA17-sul1-fosA3. Comparative genomics revealed genetic relatedness between LZ00114 and strains isolated from other regions. Furthermore, there were point mutations in pmrA (S29G, G144S), pmrB (D283G, Y358N), marR (G103S, Y137H), emrA (I219V), and emrD (G323D) of LZ00114. RT-PCR confirmed the overexpression of efflux pumps and PmrABC in LZ00114. Conclusion: This study provides valuable information for the surveillance of antimicrobial resistance and a theoretical basis for the prevention and control of colistin-resistant E. coli. There is still a need to be vigilant about the clone spread of the high-risk clone group E. coli ST410.

Tea Polyphenol Liposomes Overcome Gastric Mucus to Treat Helicobacter Pylori Infection and Enhance the Intestinal Microenvironment.

Infection with Helicobacter pylori (Hp) is one of the leading causes of stomach cancer. The ability to treat Hp infection is hampered by a lack of stomach gastric acid environment. This work introduces a nanoliposome that can rapidly adjust the gastric acid environment to ensure a drug's optimal efficacy. We introduce CaCO3@Fe-TP@EggPC nanoliposomes (CTE NLs) that are composed of Fe3+ and tea polyphenols (TPs) forming complexes on the surface of internal CaCO3 and then with lecithin producing a phospholipid bilayer on the polyphenols' outer surface. Through the action of iron-TP chelate, the phospholipid layer can fuse with the bacterial membrane to eliminate Hp. Furthermore, CaCO3 can promptly consume the excessive gastric acid, ensuring an ideal operating environment for the chelate. TPs, on the other hand, can improve the inflammation and gut microbes in the body. The experimental results show that CTE NLs can quickly consume protons in the stomach and reduce the bacterial burden by 1.2 orders of magnitude while reducing the inflammatory factors in the body. The biosafety evaluation revealed that nanoliposomes have good biocompatibility and provide a new strategy for treating Hp infection.

The Interaction between Vitamin D and Diets on Serum Lipids in Chinese Han Adolescents.

BACKGROUND: Abnormal serum lipids are closely related to cardiovascular disease. Recent studies have shown that vitamin D (VD) and vitamin D receptor (VDR) FokI polymorphism as well as dietary pattern are involved in regulating serum lipids. METHODS: According to diet pattern, adolescents were divided into high-carbohydrate (high-CHO) and non-high-carbohydrate (non-high-CHO) diet group. Based on VDR FokI polymorphism, they were assigned into TT genotype and C allele carriers. Serum lipids, glucose, and 25-hydroxyvitamin D [25(OH)D] were measured. A linear regression model was established and analyzed. RESULTS: Subjects in the non-high-CHO diet group had higher glucose than those in the high-CHO diet group. With the increasing of VD, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), cholesterol/high density lipoprotein cholesterol (TC/HDL-C), LDL-C/HDL-C decreased. TT genotype subjects had higher TC and HDL-C compared with C allele carriers. As for log triglycerides (TG), TC/HDL-C, logTG/HDL-C, there were interactions between the level of VD and diet pattern. Under the low VD level, subjects in the high-CHO diet group had higher logTG and logTG/HDL-C compared with those in the non-high-CHO diet group. However, under the medium and high level of VD, the results were opposite. In addition, under the low and medium level of VD, subjects in the high-CHO diet group had higher TC/HDL-C. CONCLUSIONS: Serum lipids are not only affected by vitamin D, VDR FokI polymorphism and dietary pattern, but also interrelated as well. The impact of diet pattern on lipids may be reversed by the high level of serum VD.

The impact of action observation and motor imagery on the aesthetic preference of Chinese calligraphy.

The creation of artwork requires motor activity. However, few empirical studies have directly explored the relationship between the experience of an artist's action and aesthetic experience. This study aimed to examine the effect of observing and imagery of the artist's action on the participants' aesthetic preferences. In Experiment 1 and 2, we took hard-pen and brush-pen Chinese calligraphy images as the stimulus, respectively, to explore the influence of action observation on the aesthetic preference by manipulating the artists' actions. The results of both Experiment 1 and 2 show that when participants observed the artists' actions, they tended to report a higher preference for calligraphy images compared with the control condition. In Experiments 3 and 4, we used instructions to manipulate the motor imagery tasks and investigated the effect of imaging the artist's action on the participants' aesthetic preferences. The results showed that both kinesthetic imagery and visual imagery increased the participants' preference. In general, our study shows that both action observation and motor imagery contribute to participants' aesthetic preferences. The results are discussed in terms of how artists' actions possibly influence the aesthetic preference of Chinese calligraphy.

Noggin Overexpression Impairs the Development of Muscles, Tendons, and Aponeurosis in Soft Palates by Disrupting BMP-Smad and Shh-Gli1 Signaling.

The roles of bone morphogenetic protein (BMP) signaling in palatogenesis were well documented in the developing hard palate; however, little is known about how BMP signaling regulates the development of soft palate. In this study, we overexpressed Noggin transgene via Osr2-cre KI allele to suppress BMP signaling in the developing soft palate. We found that BMP-Smad signaling was detected in the palatal muscles and surrounding mesenchyme. When BMP-Smad signaling was suppressed by the overexpressed Noggin, the soft palatal shelves were reduced in size with the hypoplastic muscles and the extroversive hypophosphatasia (HPP). The downregulated cell proliferation and survival in the Osr2-cre KI ;pMes-Noggin soft palates were suggested to result from the repressed Shh transcription and Gli1 activity, implicating that the BMP-Shh-Gli1 network played a similar role in soft palate development as in the hard palate. The downregulated Sox9, Tenascin-C (TnC), and Col1 expression in Osr2-cre KI ;pMes-Noggin soft palate indicated the impaired differentiation of the aponeurosis and tendons, which was suggested to result in the hypoplasia of palatal muscles. Intriguingly, in the Myf5-cre KI ;pMes-Noggin and the Myf5-cre KI ;Rosa26R-DTA soft palates, the hypoplastic or abrogated muscles affected little the fusion of soft palate. Although the Scx, Tnc, and Co1 transcription was significantly repressed in the tenogenic mesenchyme of the Myf5-cre KI ;pMes-Noggin soft palate, the Sox9 expression, and the Tnc and Col1 transcription in aponeurosis mesenchyme were almost unaffected. It implicated that the fusion of soft palate was controlled by the mesenchymal clues at the tensor veli palatini (TVP) and levator veli palatini (LVP) levels, but by the myogenic components at the palatopharyngeus (PLP) level.

The effect of action observation on aesthetic preference of Chinese calligraphy: An fMRI study.

INTRODUCTION: There is some evidence suggesting that movement perception has an effect on aesthetic experience. However, the neural mechanisms underlying the observation of creators' creative action (the process that calligraphers create calligraphy) remain unclear. METHODS: In this study, participants were scanned with fMRI while performing aesthetic judgments on Chinese calligraphy images with/without action observation. RESULTS: Behavioral results showed that both the work by the expert and novice with action observation were rated significantly higher on aesthetic preference than those without action observation. Imaging results showed that brain regions associated with perceptual, cognitive, and emotional processing were commonly activated by calligraphy images with/without action observation. However, compared with no action observation, aesthetic judgments of calligraphy images with action observation elicited stronger activation in the anterior cingulate cortex and the bilateral insula. Meanwhile, the superior parietal lobe which is associated with relevant inner action imitation, was also activated when observing the creator's action. CONCLUSIONS: Brain activation in the superior parietal lobe, anterior cingulate cortex, and the bilateral insula indicated that observing the creative action of the creators contributed to the aesthetic experience of the observer.

Over-expression of Fgf8 in cardiac neural crest cells leads to persistent truncus arteriosus.

During cardiogenesis, the outflow tract undergoes a complicated morphogenesis, including the re-alignment of the great blood vessels, and the separation of aorta and pulmonary trunk. The deficiency of FGF8 in the morphogenesis of outflow tract has been well studied, however, the effect of over-dosed FGF8 on the development of outflow tract remains unknown. In this study, Rosa26R-Fgf8 knock-in allele was constitutively activated by Wnt1-cre transgene in the mouse neural crest cells presumptive for the endocardial cushion of outflow tract. Surprisingly, Wnt1-cre; Rosa26R-Fgf8 mouse embryos exhibited persistent truncus arteriosus and died prior to E15.5. The cardiac neural crest cells in Wnt1-cre; Rosa26R-Fgf8 truncus arteriosus did not degenerate as in WT controls, but proliferated into a thickened endocardial cushion and then, blocked the blood outflow from cardiac chambers into the lungs, which resulted in the embryonic lethality. Although the spiral aorticopulmonary septum failed to form, the differentiaion of the endothelium and smooth muscle in the Wnt1-cre; Rosa26R-Fgf8 truncus arteriosus were impacted little. However, lineage tracing assay showed that the neural crest derived cells aggregated in the cushion layer, but failed to differentiate into the endothelium of Wnt1-cre; Rosa26R-Fgf8 truncus arteriosus. Further investigation displayed the reduced p-Akt and p-Erk immunostaining, and the decreased Bmp2 and Bmp4 transcription in the endothelium of Wnt1-cre; Rosa26R-Fgf8 truncus arteriosus. Our findings suggested that Fgf8 over-expression in cardiac neural crest impaired the formation of aorticopulmonary septum by suppressing the endothelial differentiation and stimulating the proliferation of endocardial cushion cells, which implicated a novel etiology of persistent truncus arteriosus.

The relationship between gestational diabetes mellitus and interleukin 1beta gene polymorphisms in southwest of China.

Gestational diabetes mellitus (GDM) is a kind of chronic inflammatory condition with carbohydrate metabolism disorder. Interleukin-1beta (IL-1ß) plays an important role in inflammatory response, but its role in GDM development remains unknown. The aim of this study was to analyze the association between Interleukin 1beta (IL1B) rs1143623 and rs16944 polymorphisms and susceptibility to GDM.In total, 300 pregnant women with GDM and 261 healthy pregnant women were included in the study. In both groups, single nucleotide polymorphism (SNP) rs1143623 and rs16944 were analyzed by using snapshot technology. IL-1ß serum values were determined by ELISA.Serum IL-1ß levels involvement in GDM development. According to the results, we found the association between the IL1B rs1143623 polymorphism and susceptibility to GDM. In further analysis, IL1B rs1143623 GG genotype had a higher level of total cholesterol (TCHO) and lower level of high density lipoprotein (HDL) in GDM patients compared with the CC/GC genotypes. However, there were no statistically significant difference between the GDM and healthy control groups in terms of rs16944 polymorphism.Our results indicated that rs1143623 in IL1B gene may lead to GDM in the southwest of china. However, no significant difference was found between GDM and rs16944. The rs1143623 genotype may significantly impact the fat metabolism, especially the levels of TCHO and HDL. We believe that our findings will contribute to understanding of the etiology and possible novel prognostic markers for GDM.

Power and pitfalls of computational methods for inferring clone phylogenies and mutation orders from bulk sequencing data.

Tumors harbor extensive genetic heterogeneity in the form of distinct clone genotypes that arise over time and across different tissues and regions in cancer. Many computational methods produce clone phylogenies from population bulk sequencing data collected from multiple tumor samples from a patient. These clone phylogenies are used to infer mutation order and clone origins during tumor progression, rendering the selection of the appropriate clonal deconvolution method critical. Surprisingly, absolute and relative accuracies of these methods in correctly inferring clone phylogenies are yet to consistently assessed. Therefore, we evaluated the performance of seven computational methods. The accuracy of the reconstructed mutation order and inferred clone groupings varied extensively among methods. All the tested methods showed limited ability to identify ancestral clone sequences present in tumor samples correctly. The presence of copy number alterations, the occurrence of multiple seeding events among tumor sites during metastatic tumor evolution, and extensive intermixture of cancer cells among tumors hindered the detection of clones and the inference of clone phylogenies for all methods tested. Overall, CloneFinder, MACHINA, and LICHeE showed the highest overall accuracy, but none of the methods performed well for all simulated datasets. So, we present guidelines for selecting methods for data analysis.

A new method for inferring timetrees from temporally sampled molecular sequences.

Pathogen timetrees are phylogenies scaled to time. They reveal the temporal history of a pathogen spread through the populations as captured in the evolutionary history of strains. These timetrees are inferred by using molecular sequences of pathogenic strains sampled at different times. That is, temporally sampled sequences enable the inference of sequence divergence times. Here, we present a new approach (RelTime with Dated Tips [RTDT]) to estimating pathogen timetrees based on a relative rate framework underlying the RelTime approach that is algebraic in nature and distinct from all other current methods. RTDT does not require many of the priors demanded by Bayesian approaches, and it has light computing requirements. In analyses of an extensive collection of computer-simulated datasets, we found the accuracy of RTDT time estimates and the coverage probabilities of their confidence intervals (CIs) to be excellent. In analyses of empirical datasets, RTDT produced dates that were similar to those reported in the literature. In comparative benchmarking with Bayesian and non-Bayesian methods (LSD, TreeTime, and treedater), we found that no method performed the best in every scenario. So, we provide a brief guideline for users to select the most appropriate method in empirical data analysis. RTDT is implemented for use via a graphical user interface and in high-throughput settings in the newest release of cross-platform MEGA X software, freely available from http://www.megasoftware.net.

Spatiotemporal disequilibrium and spillover effect of fine particulate matter across China.

Massive monitoring data requires effective statistical analysis methods. This paper aims to visualize the spatiotemporal characteristics and spillover effect of air pollutants. Ground-based PM2.5 data in 336 cities across China revealed a tough but improving situation. The PM2.5 average annual concentrations in 2016 and 2017 were 47 ± 18 µg/m3 and 44 ± 16 µg/m3 respectively, but a worse, or at least a not-improving PM2.5 situation happened in winter. A slight declining north-south disequilibrium and a growing east-west disequilibrium exhibited in 2017, along with an increasing weight of eastern and southern pollution in the proportion of the overall pollution level. North-south disequilibrium existed stably throughout the year but east-west disequilibrium was erratic. Nearly half of the cities exhibited significant spillover effects, presenting 2 clusters with spillover by high concentrations and 3 clusters with spillover by low concentrations. Most cities in Hebei, Shandong and Henan provinces showed a high but decreasing spillover effect, but increasing trend happened in the cities in Anhui and Shanxi provinces. A significant correlation appeared between the city population and PM2.5 concentration. Population density explained about 25% of the PM2.5 concentration change, and the explanation ability increased in 2017. A higher influence of population on PM2.5 concentration happened in the early stage of city development, and the influence exhibited spatial differences. The city population and PM2.5 spillover effect existed an overall positive correlation, but the population only addressed about 10% of the spillover effect change. Our findings provide important information for the joint prevention and control of air pollution in China, and the approach proposed in this paper is applicable to other fields.

The effects of high-intensity interval training versus moderate-intensity continuous training on fat loss and cardiometabolic health in pediatric obesity: A protocol of systematic review and meta-analysis.

BACKGROUND: The effects of aerobic exercise on fat loss and cardiometabolic health are well-documented, but it is unknown whether a high-intensity interval training (HIIT) elicit a greater health benefit in obese children and adolescents. METHODS: Relevant studies in Pubmed, Web of Science, Embase, the Cochrane Library, EBSCO, and CNKI will be searched for studies with language restriction in English and Chinese, which were published from inception to December 1, 2018. Only randomized controlled trials of HIIT on pediatric obesity will be included, and observational studies, prospective cohort studies, and systematic reviews will be excluded. Two reviewers will independently screen the studies; risk of bias assessment and data extraction, and the results are inconsistent when discussed or resolved by a third reviewer. Data analysis and synthesis will be completed by the Revman 5.3 software and Stata 12.0 software. This study will be conducted by following the guideline of the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols. CONCLUSION: This study will be conducted by previously published data, thus ethics approval is not required. This finding will be published in a related peer-reviewed journal and present it at international conferences. PROSPERO REGISTRATION NUMBER: CRD42018111308.