Erratum to Clinical management and survival outcomes of patients with different molecular subtypes of diffuse gliomas in China(2011-2017):a multicenter retrospective study from CGGA

In the published version of Figure 21,an error appeared in Figure 2C on page 1468.In Figure 2C,the Kaplan-Meier estimation of the overall survival of patients with recurrent DG classified according to molecular subtypes was mistakenly covered by the curves of patients with primary DGs during the figure layout process,while the number statistic under the figure is correct.Figure 2C has been updated to correct this mistake.The error does not affect the conclusions of this article.We apologize for the error and for any confusion that it might have caused.

Clinical management and survival outcomes of patients withdifferent molecular subtypes of diffuse gliomas in China(2011–2017):a multicenter retrospective study from CGGA

Objective:We aimed to summarize the clinicopathological characteristics and prognostic features of various molecular subtypes of diffuse gliomas(DGs)in the Chinese population.Methods:In total,1,418 patients diagnosed with DG between 2011 and 2017 were classified into 5 molecular subtypes according to the 2016 WHO classification of central nervous system tumors.The IDH mutation status was determined by immunohistochemistry and/or DNA sequencing,and 1p/19q codeletion was detected with fluorescence in situ hybridization.The median clinical follow-up time was 1,076 days.T-tests and chi-square tests were used to compare clinicopathological characteristics.Kaplan‒Meier and Cox regression methods were used to evaluate prognostic factors.Results:Our cohort included 15.5%lower-grade gliomas,IDH-mutant and 1p/19q-codeleted(LGG-IDHm-1p/19q);18.1%lowergrade gliomas,IDH-mutant(LGG-IDHm);13.1%lower-grade gliomas,IDH-wildtype(LGG-IDHwt);36.1%glioblastoma,IDHwildtype(GBM-IDHwt);and 17.2%glioblastoma,IDH-mutant(GBM-IDHm).Approximately 63.3%of the enrolled primary gliomas,and the median overall survival times for LGG-IDHm,LGG-IDHwt,GBM-IDHwt,and GBM-IDHm subtypes were 75.97,34.47,11.57,and 15.17 months,respectively.The 5-year survival rate of LGG-IDHm-1p/19q was 76.54%.We observed a significant association between high resection rate and favorable survival outcomes across all subtypes of primary tumors.We also observed a significant role of chemotherapy in prolonging overall survival for GBM-IDHwt and GBM-IDHm,and in prolonging post-relapse survival for the 2 recurrent GBM subtypes.Conclusions:By controlling for molecular subtypes,we found that resection rate and chemotherapy were 2 prognostic factors associated with survival outcomes in a Chinese cohort with DG.

Epidemiological characteristics and genetic alterations in adult diffuse glioma in East Asianpopulations

Understanding the racial specificities of diseases—such as adult diffuse glioma,the most common primary malignant tumor of the central nervous system—is a critical step toward precision medicine.Here,we comprehensively review studies of gliomas in East Asian populations and other ancestry groups to clarify the racial differences in terms of epidemiology and genomic characteristics.Overall,we observed a lower glioma incidence in East Asians than in Whites;notably,patients with glioblastoma had significantly younger ages of onset and longer overall survival than the Whites.Multiple genome-wide association studies of various cohorts have revealed single nucleotide polymorphisms associated with overall and subtype-specific glioma susceptibility.Notably,only 3 risk loci—5p15.33,11q23.3,and 20q13.33—were shared between patients with East Asian and White ancestry,whereas other loci predominated only in particular populations.For instance,risk loci 12p11.23,15q15-21.1,and 19p13.12 were reported in East Asians,whereas risk loci 8q24.21,1p31.3,and 1q32.1 were reported in studies in White patients.Although the somatic mutational profiles of gliomas between East Asians and non-East Asians were broadly consistent,a lower incidence of EGFR amplification in glioblastoma and a higher incidence of 1p19q-IDH-TERT triple-negative low-grade glioma were observed in East Asian cohorts.By summarizing large-scale disease surveillance,germline,and somatic genomic studies,this review reveals the unique characteristics of adult diffuse glioma among East Asians,to guide clinical management and policy design focused on patients with East Asian ancestry.

Synthesis and Performance Evaluation of Organic Bentonite Modifier Dimethyldistearylammonium Bromide (DODMAB)

Dimethyldistearylammonium Bromide (DODMAB) is a bentonite modifier with good performance. In this experiment, 1-Bromooctadecane is the raw material, and completes tertiary amination and quaternization successively by changing the condition of experiment. The result is that the productivity can achieve 78.94% in the synthesis of DODMAB. It has been used in the experiment of bentonite modification and achieves good results;compared with using trimethylstearylammonium bromide as the organic modifier, the synthetic organic bentonite has better performance than the common organic modifier when used in the oil base drilling fluid of oilfield operation.

Review on recent progress in on-line monitoring technology for atmospheric pollution source emissions in China

Emissions from mobile sources and stationary sources contribute to atmospheric pollution in China,and its components,which include ultrafine particles(UFPs),volatile organic compounds(VOCs),and other reactive gases,such as NH3and NOx,are the most harmful to human health.China has released various regulations and standards to address pollution from mobile and stationary sources.Thus,it is urgent to develop online monitoring technology for atmospheric pollution source emissions.This study provides an overview of the main progress in mobile and stationary source monitoring technology in China and describes the comprehensive application of some typical instruments in vital areas in recent years.These instruments have been applied to monitor emissions from motor vehicles,ships,airports,the chemical industry,and electric power generation.Not only has the level of atmospheric environment monitoring technology and equipment been improving,but relevant regulations and standards have also been constantly updated.Meanwhile,the developed instruments can provide scientific assistance for the successful implementation of regulations.According to the potential problem areas in atmospheric pollution in China,some research hotspots and future trends of atmospheric online monitoring technology are summarized.Furthermore,more advanced atmospheric online monitoring technology will contribute to a comprehensive understanding of atmospheric pollution and improve environmental monitoring capacity.

Somatic GJA4 mutation in intracranial extra-axial cavernous hemangiomas

Objective Extra-axial cavernous hemangiomas(ECHs)are sporadic and rare intracranial occupational lesions that usually occur within the cavernous sinus.The aetiology of ECHs remains unknown.Methods Whole-exome sequencing was performed on ECH lesions from 12 patients(discovery cohort)and droplet digital polymerase-chain reaction(ddPCR)was used to confirm the identified mutation in 46 additional cases(validation cohort).Laser capture microdissection(LCM)was carried out to capture and characterise subgroups of tissue cells.Mechanistic and functional investigations were carried out in human umbilical vein endothelial cells and a newly established mouse model.Results We detected somatic GJA4 mutation(c.121G>T,p.G41C)in 5/12 patients with ECH in the discovery cohort and confirmed the finding in the validation cohort(16/46).LCM followed by ddPCR revealed that the mutation was enriched in lesional endothelium.In vitro experiments in endothelial cells demonstrated that the GJA4 mutation activated SGK-1 signalling that in turn upregulated key genes involved in cell hyperproliferation and the loss of arterial specification.Compared with wild-type littermates,mice overexpressing the GJA4 mutation developed ECH-like pathological morphological characteristics(dilated venous lumen and elevated vascular density)in the retinal superficial vascular plexus at the postnatal 3 weeks,which were reversed by an SGK1 inhibitor,EMD638683.Conclusions We identified a somatic GJA4 mutation that presents in over one-third of ECH lesions and proposed that ECHs are vascular malformations due to GJA4-induced activation of the SGK1 signalling pathway in brain endothelial cells.

Intratumor heterogeneity,microenvironment,and mechanisms of drug resistance in glioma recurrence and evolution

Glioma is the most common lethal tumor of the human brain.The median survival of patients with primary World Health Organization grade IV glioma is only 14.6 months.The World Health Organization classification of tumors of the central nervous system categorized gliomas into lower-grade gliomas and glioblastomas.Unlike primary glioblastoma that usually develop de novo in the elderly,secondary glioblastoma enriched with an isocitrate dehydrogenase mutant typically progresses from lower-grade glioma within 5-10 years from the time of diagnosis.Based on various evolutional trajectories brought on by clonal and subclonal alterations,the evolution patterns of glioma vary according to different theories.Some important features distinguish the normal brain from other tissues,e.g.,the composition of the microenvironment around the tumor cells,the presence of the blood-brain barrier,and others.The underlying mechanism of glioma recurrence and evolution patterns of glioma are different from those of other types of cancer.Several studies correlated tumor recurrence with tumor heterogeneity and the immune microenvironment.However,the detailed reasons for the progression and recurrence of glioma remain controversial.In this review,we introduce the different mechanisms involved in glioma progression,including tumor heterogeneity,the tumor microenvironment and drug resistance,and their pre-clinical implements in clinical trials.This review aimed to provide new insights into further clinical strategies for the treatment of patients with recurrent and secondary glioma.

Deciphering Brain Complexity Using Single-cell Sequencing

The human brain contains billions of highly differentiated and interconnected cells that form intricate neural networks and collectively control the physical activities and high-level cognitive functions,such as memory,decision-making,and social behavior.Big data is required to decipher the complexity of cell types,as well as connectivity and functions of the brain.The newly developed single-cell sequencing technology,which provides a comprehensive landscape of brain cell type diversity by profiling the transcriptome,genome,and/or epigenome of individual cells,has contributed substantially to revealing the complexity and dynamics of the brain and providing new insights into brain development and brain-related disorders.In this review,we first introduce the progresses in both experimental and computational methods of single-cell sequencing technology.Applications of single-cell sequencing-based technologies in brain research,including cell type classification,brain development,and brain disease mechanisms,are then elucidated by representative studies.Lastly,we provided our perspectives into the challenges and future developments in the field of single-cell sequencing.In summary,this mini review aims to provide an overview of how big data generated from single-cell sequencing have empowered the advancements in neuroscience and shed light on the complex problems in understanding brain functions and diseases.

Real-world gaseous emission characteristics of natural gas heavy-duty sanitation trucks

As compared to conventional diesel heavy-duty vehicles,natural gas vehicles have been proved to be more eco-friendly due to their lower production of greenhouse gas and pollu-tant emissions,which are causing enormous adverse effects on global warming and air pol-lution.However,natural gas vehicles were rarely studied before,especially through on-road measurements.In this study,a portable emission measurement system(PEMS)was em-ployed to investigate the real-world emissions of nitrogen oxides(NO_(x))(nitrogen monoxide(NO),nitrogen dioxide(NO_(2))),total hydrocarbons(THC),carbon monoxide(CO),and carbon dioxide(CO_(2))from two liquified natural gas(LNG)China V heavy-duty cleaning sanitation trucks with different weight.Associated with the more aggressive driving behaviors,the ve-hicle with lower weight exhibited higher CO_(2)(3%)but lower NO_(x)(48.3%)(NO_(2)(78.2%)and NO(29.4%)),CO(44.8%),and THC(3.7%)emission factors.Aggressive driving behaviors were also favorable to the production of THC,especially those in the medium-speed range but sig-nificantly negative to the production of CO and NO_(2),especially those in the low-speed range with high engine load.In particular,the emission rate ratio of NO_(2)/NO decreased with the increase of speed/scaled tractive power in different speed ranges.

Ambulatory blood pressure monitoring for the management of hypertension

Ambulatory blood pressure monitoring(ABPM)has become indispensable in the current management of hypertension.ABPM is particularly useful in the accurate diagnosis of hypertension.Its diagnostic thresholds had been recently established based on hard clinical outcomes.Cross-classification of patients according to office and ambulatory blood pressure identifies white-coat,masked,and sustained hypertension.ABPM is also useful in cardiovascular(CV)risk assessment.It provides information on daytime and nighttime blood pressure and circadian rhythm,particularly nighttime blood pressure dipping.Nighttime blood pressure is predictive of CV risk independent of office and daytime blood pressure.Isolated nocturnal hypertension is a special form of masked hypertension,with normal daytime but elevated nocturnal blood pressure.It also helps in the evaluation of blood pressure fluctuation and variation,such as morning blood pressure surge and reading-to-reading blood pressure variability.ABPM may derive several other indexes,such as ambulatory blood pressure index and salt sensitivity index,which may be useful in CV evaluations.

SEQUENCE-BASED PROTEIN-PROTEIN INTERACTION PREDICTION VIA SUPPORT VECTOR MACHINE

This paper develops sequence-based methods for identifying novel protein-protein interactions （PPIs） by means of support vector machines （SVMs）. The authors encode proteins ont only in the gene level but also in the amino acid level, and design a procedure to select negative training set for dealing with the training dataset imbalance problem, i.e., the number of interacting protein pairs is scarce relative to large scale non-interacting protein pairs. The proposed methods are validated on PPIs data of Plasmodium falciparum and Escherichia coli, and yields the predictive accuracy of 93.8% and 95.3%, respectively. The functional annotation analysis and database search indicate that our novel predictions are worthy of future experimental validation. The new methods will be useful supplementary tools for the future proteomics studies.

Depressing defocusing effect in microscopy by bi-orthogonal wavelet transform

For different dimensions, heights and irregular shapes, small and large particles cannot be viewed simultaneously as sharp images under the microscope due to optical defocusing effects. Bi-orthogonal wavelet transform is used in this paper to depress such defocusing effect by merging the wavelet coefficients of the image series. The algorithm is presented in detail, using SWE（13,7） and CDF（2,2）, and a few particle images are provided to validate the proposed method.

An information theoretic method to identify combinations of genomic alterations that promote glioblastoma

Tumors are the result of accumulated genomic alterations that cooperate synergistically to produce uncontrollable cell growth.Although identifying recurrent alterations among large collections of tumors provides a way to pinpoint genes that endow a selective advantage in oncogenesis and progression,it fails to address the genetic interactions behind this selection process.A non-random pattern of co-mutated genes is evidence for selective forces acting on tumor cells that harbor combinations of these genetic alterations.Although existing methods have successfully identified mutually exclusive gene sets,no current method can systematically discover more general genetic relationships.We develop Genomic Alteration Modules using Total Correlation(GAMToC),an information theoretic frameworkthat integrates copynumberandmutation datato identify genemodules with any non-randompattern of joint alteration.Additionally,wepresent theSeed-GAMToCprocedure,which uncoversthe mutational context of any putative cancer gene.The software is publicly available.Applied to glioblastoma multiforme samples,GAMToC results show distinct subsets of co-occurring mutations,suggesting distinct mutational routes to cancer and providing new insight into mutations associated with proneural,proneural/G-CIMP,and classical types of the disease.The results recapitulate known relationships such as mutual exclusive mutations,place these alterations in the context of other mutations,and find more complex relationships such as conditional mutual exclusivity.

RECOGNITION OF STRUCTURE SIMILARITIES IN PROTEINS

Protein fold structure is more conserved than its amino acid sequence and closely associated with biological function, so calculating the similarity of protein structures is a fundamental problem in structural biology and plays a key role in protein fold classification, fold function inference, and protein structure prediction. Large progress has been made in recent years in this field and many methods for considering structural similarity have been proposed, including methods for protein structure comparison, retrieval of protein structures from databases, and ligand binding site comparison. Most of those methods can be available on the World Wide Web, but evaluation of all the methods is still a hard problem. This paper summarizes some popular methods and latest methods for structure similarities, including structure alignment, protein structure retrieval, and ligand binding site alignment.

REMARKS ON NETWORK COMMUNITY PROPERTIES

This paper discusses a popular community definition in complex network research in terms of the conditions under which a community is minimal, that is, the community cannot be split into several smaller communities or split and reorganized with other network elements into new communities. The result provides a base on which further optimization computation of the quantitative measure for community identification can be realized.

CELLO:a longitudinal data analysis toolbox untangling cancer evolution

The complex pattern of cancer evolution poses a huge challenge to precision oncology.Longitudinal sequencing of tumor samples allows us to monitor the dynamics of mutations that occurred during this clonal evolution process.Here,we present a versatile toolbox,namely CELLO(Cancer EvoLution for Longitudinal data),accompanied with a step-by-step tutorial,to exemplify how to profile,analyze and visualize the dynamic change of somatic mutational landscape using longitudinal genomic sequencing data.Moreover,we customize the hypermutation detection module in CELLO to adapt targeted-DNA and whole-transcriptome sequencing data,and verify the extensive applicability of CELLO in published longitudinal datasets from brain,bladder and breast cancers.The entire tutorial and reusable programs in MATLAB,R and docker versions are open access at https://github.com/WaiigLabHKUST/CELLO.

MET fusions and splicing variants convergently defne a subgroup of glioma sensitive to MET inhibitors

Purpose:Our previous study has shown that PTPRZ1-MET(ZM)fusion is a viable target for MET inhibitors in gliomas.However,the diversity and prevalence of somatic MET alterations in difuse gliomas are still elusive and need to be extensively characterized for identifying novel therapeutic targets.Methods:Totally,1,350 glioma patients and 31 patient-derived cells were collected from the Chinese Glioma Genome Atlas(CGGA)and published data.All kinds of MET fusions and/or splicing variants(MET F/SVs)were identifed by bioinformatical methods.Single-cell RNA sequencing(scRNA-seq)were used for validation.In vitro experiments of drug resistance were conducted for the possibility of MET-targeted treatment.Results:MET F/SVs but not genomic amplifcation,were highly enriched in the secondary glioblastomas(sGBM)and marked worse prognosis.Further molecular and scRNA-seq analysis revealed that MET F/SVs were induced in the course of glioma evolution and highly associated with MET overexpression.Subsequent in vitro and the clinical study showed that cells and patients harboring MET F/SVs have better response to MET inhibitors.Conclusion:Our fndings expanded the percentage of gliomas with abnormal MET alterations and suggested that a subgroup of gliomas harboring MET F/SVs may beneft from MET-targeted therapy.