Partial Fusion (F) Gene Analysis of Newcastle Disease Virus Detected in Pakistan during 2021-2022

Newcastle disease (ND) virus is a leading threat to commercial and domestic poultry in Pakistan. The virus infects and constitutes irreversible impairment to the nervous system, damages the respiratory system, and marks severe gastrointestinal lesions leading to heavy mortality in short-living birds and substantial losses in layers and breeders. The continuous emergence and evolution of the virus made it inclined to evade the humoral response and indirectly the circumvention of artificial active immunization. Newcastle disease is caused by the orthoavula genus of the paramyxoviridae family and has shown high genetic diversity even in their genotypes while information regarding enzootic trends of the virus is scanty in Pakistan. A total of 40 tracheal samples of NDV were collected from different commercial broiler farms and 11 isolates of NDV were identified. In the current study, we determined the genetic diversity of the Newcastle disease virus based on the partial sequencing of the fusion protein gene available in the NCBI database. Genetic analysis showed that seven isolates belonged to class I genotype VII and four belonged to class II genotype II. Interestingly, two isolates had epidemiological connections with vaccine-like class II genotype II. Our findings, concerning the recent outbreaks of class I genotype VII and class II genotype II of NDV in vaccinated commercial flocks, suggest possible potential partial mutations in the fusion protein gene. Genetic diversity and formation of the new cleavage site in an important neutralizing protein of wild strain are linked with the potency of artificial active immunization and a major cause of vaccine failure.

Novel Metrics for Mutation Analysis

A measure of the“goodness”or efficiency of the test suite is used to determine the proficiency of a test suite.The appropriateness of the test suite is determined through mutation analysis.Several Finite State Machine(FSM)mutants are produced in mutation analysis by injecting errors against hypotheses.These mutants serve as test subjects for the test suite(TS).The effectiveness of the test suite is proportional to the number of eliminated mutants.The most effective test suite is the one that removes the most significant number of mutants at the optimal time.It is difficult to determine the fault detection ratio of the system.Because it is difficult to identify the system’s potential flaws precisely.In mutation testing,the Fault Detection Ratio(FDR)metric is currently used to express the adequacy of a test suite.However,there are some issues with this metric.If both test suites have the same defect detection rate,the smaller of the two tests is preferred.The test case(TC)is affected by the same issue.The smaller two test cases with identical performance are assumed to have superior performance.Another difficulty involves time.The performance of numerous vehicles claiming to have a perfect mutant capture time is problematic.Our study developed three metrics to address these issues:FDR/|TS|,FDR/|TC|,and FDR/|Time|;In this context,most used test generation tools were examined and tested using the developed metrics.Thanks to the metrics we have developed,the research contributes to eliminating the problems related to performance measurement by integrating the missing parameters into the system.

Comparative analysis of dideoxy sequencing,the KRAS StripAssay and pyrosequencing for detection of KRAS mutation

AIM:To compare the differences between dideoxy sequencing/KRAS StripAssay/pyrosequencing for detection of KRAS mutation in Chinese colorectal cancer (CRC) patients.METHODS:Formalin-f ixed, paraff in-embedded (FFPE) samples with tumor cells ≥ 50% were collected from 100 Chinese CRC patients at Beijing Cancer Hospital. After the extraction of genome DNA from FFPE samples, fragments contained codons 12 and 13 of KRAS exon 2 were amplified by polymerase chain reaction and analyzed by dideoxy sequencing, the KRAS Strip Assay and pyrosequencing. In addition, the sensitivities of the 3 methods were compared on serial dilutions (contents of mutant DNA: 100%,50%,20%, 5%,10%, 5%,1%,0%) of A549 cell line DNA (carrying the codon 12 Gly>Ser mutation) into wild-type DNA (human normal intestinal mucosa). The results of dideoxy sequencing,the KRAS StripAssay and pyrosequencing were analyzed by Chromas Software, Collector forKRAS Strip Assay and the pyrosequencing PyroMarkTM Q24 system, respectively.RESULTS: Among 100 patients, KRAS mutations were identif ied in 34%, 37% and 37% of patients by dideoxy sequencing, the KRAS StripAssay and pyrosequencing, respectively. The sensitivity was highest with the KRAS Strip Assay (1%), followed by pyrosequencing (5%), and dideoxy sequencing was lowest (15%). Six different mutation types were found in this study with 3 main mutations Gly12 Asp (GGT>GAT), Gly12 Val (GGT>GTT) and Gly13 Asp (GGC>GAC). Thirty-three patients were identifi ed to have KRAS mutations by the 3 methods, and a total of 8 patients had conflicting results between 3 methods: 4 mutations not detected by dideoxy sequencing and the KRAS StripAssay were identified by pyrosequencing; 3 mutations not detected by dideoxy sequencing and pyrosequencing were identif ied by the KRAS StripAssay; and 1 mutation not detected by pyrosequencing was conf irmed by dideoxy sequencing and the KRAS StripAssay. Among these discordant results, the results identif ied by dideoxy sequencing were consistent either with the KRAS StripAssay or with pyrosequencing, which indicated that the accuracy of dideoxy sequencing was high. CONCLUSION: Taking a worldwide view of reports and our results,dideoxy sequencing remains the most popular method because of its low cost and high accuracy.

Clinical classification and gene mutation of Chinese probands with Charcot-Marie-Tooth disease Analysis of 57 cases

Charcot-Marie-Tooth （CMT） disease is the most common inherited peripheral neuropathic disorder. CMT is clinically and genetically heterogeneous. To date, 27 genes associated with the disease have been cloned. The present study carried out clinical classification according to clinical, electrophysiological and pathological features, conducted inheritance classification according to inheritance patterns, and performed mutation analysis of 13 CMT disease genes （PMP22, CX32, HSPB1, MNF2, MPZ, HSPB8, GDAP1, NFL, EGR2, SIMPLE, RAB7, LMNA, MTMR2） in 57 Chinese probands with CMT. Five cases of AD-CMT1 and 13 cases of sporadic CMT1 were diagnosed as CMT1A; five cases of X-CMT1, one case of X-CMT2 and one case of sporadic CMT1 were diagnosed as CMTXl; four cases of AD-CMT2 were diagnosed as CMT2F; one case of AD-CMT2 and one case of sporadic CMT2 were diagnosed as CMT2A2; one case of AD-CMT2 was diagnosed as CMT2L; one case of AD-CMT2 was diagnosed as CMT2J; one case of AR-CMT1 was diagnosed as CMT4A. Among the 57 CMT probands, seven genotypes were determined among 34 patients, with a detection rate of 59.6%. The results indicated that the clinical classification and inheritance classification are indispensable for selecting potential disease genes for mutation detection, and for efficient molecular diagnosis.

Mutation Analysis of IgVH Gene in B-Cell Chronic Lymphocytic Leukemia

Summary: The variable heavy chain region (VH) genes of 3 untreated patients with B cell chronic lymphocytic leukemia (B CLL) were cloned and analyzed. The VH family used was VH3 11, VH3 72 and VH3 33. More than 2 % difference from the corresponding germline gene was detected in all the 3 obtained potential functional genes (average 16.7). Mutation pattern analysis indicated evidence of antigen selective pressure observed in 1 of 3 cases. Our findings suggested that the tumor cells originate from post GC cells.

Analysis on Changing Trends of Temperature and Precipitation in Huanren County over the Past 58Years

Based on data of temperature and precipitation in Huanren County from 1953 to 2010, linear trend analysis and mutation detection of temperature and precipitation sequence were carried out using linear trend, Mann-Kendall detection and dryness of the de Martonne method. The results showed that during 1953-2010, annual average temperature, annual average maximum and minimum temperature in Huanren County showed an increasing trend; annual precipitation showed a decreasing trend; there was a downward trend in annual dryness. The mutation of annu- al average temperature, annual average maximum and minimum temperature appeared in 1978, 1987 and 1982 respectively; there was no mutation of annual precipitation and dryness. On the whole, the climate of Huanren County tended to be warm and dry over the past 58 years.

Analysis on the Variation of Rainfall Data from Guilin Weather Station during 1957-2007

[Objective] The research aimed to study the variation of rainfall data from Guilin Weather Station during 1957-2007.[Method] Based on the daily rainfall data in Guilin during 1957-2007,the trend,period and mutation of precipitation in Guilin in 51 years were analyzed by using the trend analysis,wavelet analysis and Mann-Kendall non-parameter statistics test method.[Result] The rainfall in Guilin in 51 years presented the rising trend.The rainfall variation was same in the first,second and third quarters of most years,except in the individual year.The rainfall in the fourth quarter had the decrease trend,and the variation was obvious in each year.It illustrated that the rainfall variation in winter was very unstable and had the decrease trend in recent years.But as a whole,the variation of total rainfall in Guilin wasn’t obvious and had the rise trend.It illustrated that the climate variation in Guilin in 51 years wasn’t obvious.The wavelet analysis showed that the rainfall variation in Guilin had 15-year big period and the small period of 2-3 years.Mann-Kendall non-parameter statistics test showed that the mutation situation of total rainfall in Guilin in 51 years wasn’t obvious.But the mutation situations in the second and third quarters were more.The variation in recent 10 years was the most obvious.Maybe it was affected by the global climate variation.[Conclusion] The research provided the theory basis for analyzing the climate variation in Guilin.

RET proto-oncogene mutation analysis in a pedigree with multiple endocrine neoplasia 2A

Objective To discuss clinical diagnosis and treatment of multiple endocrine neoplasia ( MEN) 2A,and report the mutation of RET proto-oncogene in a pedigree of three patients with MEN 2A. Methods Bilateral adrenalectomy was performed on two of the three

Gene targeted and immune therapies for nodal and gastrointestinal follicular lymphomas

Follicular lymphoma(FL)is the most common indolent B-cell lymphoma(BCL)globally.Recently,its incidence has increased in Europe,the United States,and Asia,with the number of gastrointestinal FL cases expected to increase.Genetic abnormalities related to t(14;18)translocation,BCL2 overexpression,NF-κB pathway-related factors,histone acetylases,and histone methyltransferases cause FL and enhance its proliferation.Meanwhile,microRNAs are commonly used in diagnosing FL and predicting patient prognosis.Many clinical trials on novel therapeutics targeting these genetic abnormalities and immunomodulatory mechanisms have been conducted,resulting in a marked improvement in therapeutic outcomes for FL.Although developing these innovative therapeutic agents targeting specific genetic mutations and immune pathways has provided hope for curative options,FL treatment has become more complex,requiring combinatorial therapeutic regimens.However,optimal treatment combinations have not yet been achieved,highlighting the importance of a complete understanding regarding the pathogenesis of gastrointestinal FL.Accordingly,this article reviews key research on the molecular pathogenesis of nodal FL and novel therapies targeting the causative genetic mutations.Moreover,the results of clinical trials are summarized,with a particular focus on treating nodal and gastrointestinal FLs.

Characteristics of the dynamic changes in active accumulated temperature in Sichuan,China in the last 51 years against the background of climate change

It is of utmost necessity to understand the dynamics of regional active accumulated temperature(AAT)to cope with the negative impacts of global warming on agroforestry development and food security and to provide a real-time and effective reference basis for regional agroforestry planning.The daily temperature data from 30 meteorological stations in Sichuan Province from 1970 to 2020,and sea surface temperature(SST)index data from the Atlantic Multiphase Oscillation(AMO)and Pacific Decadal Oscillation(PDO)were used for the study.Sichuan Province was divided into the western region(WS)and the eastern region(ES),considering 1000 m above sea level as the boundary.The spatiotemporal characteristics of≥0℃ and≥10℃ active accumulated temperature(AAT0,AAT10)in WS and ES were analyzed comprehensively using 5-day average sliding,empirical orthogonal function(EOF),ensemble empirical mode decomposition(EEMD),and multiple mutation tests.The results show that(1)AAT0 and AAT10 of WS ranged from 3034℃ to 3586℃ and 1971℃ to 2636℃,respectively,while the AAT0 and AAT10 of ES ranged from 5863℃ to 6513℃ and 4847℃ to 5875℃,respectively.The period around 1997 was a significant abrupt change,and the AAT in the province generally increased during the subsequent time period(2)AAT in the study area is mainly driven by the fluctuations of AMO,as reflected by the low-to-high variation of AAT coinciding with the jump of the cold-to-warm phase of AMO.Considering different time scale fluctuations in the past 51 years,the major cycle for both AAT0 and AAT10 in WS is 3.40 a,while the major cycles in ES are 3.64 a and 3.19 a,respectively with a sub-cycle of 7.29 a.AAT fluctuation has an insignificant periodic characteristic of 25.50 a on the interdecadal scale(3)The spatial heterogeneity of AAT in WS is prominent and is mainly reflected by the significantly warm conditions in the south of the WS region and relatively slight warm conditions in the north,as well as by the isolated cooling area in the form of"freezing point",i.e.,Xiaojin county.In contrast,the spatial variability of AAT in ES is more or less consistent,with the warming areas concentrated in the foothills of the western edge of the basin and a slight increase in AAT observed in the central part of the basin.

Investigation of Single and Multiple Mutations Prediction Using Binary Classification Approach

The mutation is a critical element in determining the proteins’stability,becoming a core element in portraying the effects of a drug in the pharmaceutical industry.Doing wet laboratory tests to provide a better perspective on protein mutations is expensive and time-intensive since there are so many potential muta-tions,computational approaches that can reliably anticipate the consequences of amino acid mutations are critical.This work presents a robust methodology to analyze and identify the effects of mutation on a single protein structure.Initially,the context in a collection of words is determined using a knowledge graph for feature selection purposes.The proposed prediction is based on an easier and sim-pler logistic regression inferred binary classification technique.This approach can able to obtain a classification accuracy(AUC)Area Under the Curve of 87%when randomly validated against experimental energy changes.Moreover,for each cross-fold validation,the precision,recall,and F-Score are presented.These results support the validity of our strategy since it performs the vast majority of prior studies in this domain.

沈阳市59年来气温变化及其突变性分析(英文)

In this paper,based on the observation data of air temperature during 1951-2009 in Shenyang,the interannual and interdecadal variation of annual average temperature,maximum and minimum temperature in Shenyang were conducted the statistical analysis by means of linear trend estimation and mutation detection by using Mann-Kendall method.As was demonstrated in the results,the annual average temperature,maximum and minimum temperature in Shenyang showed an upward trend,whose linear tendency rate was 0.231,0.181 and 0.218 respectively.The increment trend of annual average temperature,maximum and minimum temperature was extremely clear.The increase in minimum temperature was more significant than that in mean temperature and maximum temperature.The abrupt change point of annual mean temperature in Shenyang appeared in 1981;the abrupt change point of annual mean maximum temperature appeared in 1994;the annual mean minimum temperature underwent mutation in 1978.

Gastrointestinal stromal tumor metastasis at the site of a totally implantable venous access port insertion:A rare case report

BACKGROUND The totally implantable venous access port(TIVAP)is an important device in patients for injecting blood products,parenteral nutrition or antineoplastic chemotherapy.Metastatic spread at the site of the insertion of a TIVAP is extremely rare.CASE SUMMARY We report the case of 33-year-old male with advanced gastrointestinal stromal tumor(GIST)who underwent radical tumor resection after neoadjuvant imatinib therapy.However,a solitary GIST metastasis at the site of a TIVAP insertion developed during adjuvant imatinib treatment.Mutational analysis showed secondary mutation in KIT exon 13(V564 A),which is resistant to imatinib treatment.To our knowledge,this is the first case report of a patient with advanced GIST developing GIST metastasis at the site of a TIVAP insertion.CONCLUSION This case highlights that when a patient with advanced,high metastatic GIST requires TIVAP insertion,we should realize that there is a risk of developing tumor metastasis at the site of a TIVAP insertion.

Gastric schwannoma treated by endoscopic full-thickness resection and endoscopic purse-string suture:A case report

BACKGROUND Schwannomas,also known as neurinomas,are tumors that derive from Schwann cells.Gastrointestinal schwannomas are extremely rare,but the stomach is the most common site.Gastric schwannomas are usually asymptomatic.Endoscopy and imaging modalities might offer useful preliminary diagnostic information.However,to diagnose schwannoma,the immunohistochemical positivity for S-100 protein is essential,whereas CD117,CD34,SMA,desmin,and DOG-1 are negative.CASE SUMMARY A 45-year-old female was found to have a gastric mass during a medical examination,which was diagnosed as a gastric schwannoma.We performed endoscopic full-thickness resection and endoscopic purse-string suture.Pathology and immunohistochemical staining confirmed the diagnosis of gastric schwannoma through the positivity of S-100 protein.Furthermore,to exclude the misdiagnosis of gastrointestinal stromal tumor,we performed a mutational detection of the c-Kit and PDGFRA genes.Postoperative follow-up revealed that the patient recovered well.CONCLUSION Immunohistochemical staining is essential for the diagnosis of schwannoma.Endoscopic full-thickness resection is an effective treatment method for gastric schwannoma.

Identification of speckle-type POZ protein somatic mutations in African American prostate cancer

The speckle-type POZ protein （SPOP） is a tumor suppressor in prostate cancer （PCa）. SPOP somatic mutations have been reported in up to 15% of PCa of those of European descent. However, the genetic roles of SPOP in African American （AA）-PCa are currently unknown. We sequenced the SPOP gene to identify somatic mutations in 49 AA prostate tumors and identified three missense mutations （p.Y87C, p.F102S, and p.G111E） in five AA prostate tumors （10%） and one synonymous variant （p.11061） in one tumor. Intriguingly, all of mutations and variants clustered in exon six, and all of the mutations altered conserved amino acids. Moreover, two mutations （p.F102S and p.G111E） have only been identified in AA-PCa to date. Quantitative real-time polymerase chain reaction analysis showed a lower level of SPOP expression in tumors carrying SPOP mutations than their matched normal prostate tissues. In addition, SPOP mutations and novel variants were detected in 5 of 27 aggressive PCa and one of 22 less aggressive PCa （P 〈 0.05）. Further studies with increased sample size are needed to validate the clinicopathological significance of these SPOP mutations in AA-PCa.

Identifying Driver Genes Mutations with Clinical Significance in Thyroid Cancer

Advances in technology are enabling gene mutations in papillary thyroid carcinoma(PTC)to be analyzed and clinical outcomes,such as recurrence,to be predicted.To date,the most common genetic mutation in PTC is in BRAF kinase(BRAF).However,whether mutations in other genes coincide with those in BRAF remains to be clarified.The aim of this study was to find mutations in other genes that co-exist with mutated BRAF,and to analyze their frequency and clinical relevance in PTC.Clinical and genetic data were collected from 213 PTC patients with a total of 36,572 mutation sites in 735 genes.After matching with genes from PTC entries in a global database(NCBI Gene),69 genes with mutations in coding regions were chosen for further study.Through frequency-based analysis,we identified commonly mutated genes co-existing with mutated BRAF and,using the mutation count correlation matrix(MCCM)method,analyzed their incidence according to age and gender.We designed Chord diagrams to reveal gene relationships concerning age and gender,and found that mutations in ALK,ATM,COL1A1,MSTIR,PRKCA,and WNK1 most commonly coincide with mutated BRAF,followed by APC,AURKA,and AURKB.These findings provide further insight into the genetic profile of PTC.

Missed colorectal cancers in a fecal immunochemical test-based screening program: Molecular profiling of interval carcinomas

BACKGROUND For optimizing fecal immunochemical test(FIT)-based screening programs,reducing the rate of missed colorectal cancers(CRCs)by FIT(FIT-interval CRCs)is an important aspect.Knowledge of the molecular make-up of these missed lesions could facilitate more accurate detection of all(precursor)lesions.AIM To compare the molecular make-up of FIT-interval CRCs to lesions that are detected by FIT[screen-detected CRCs(SD-CRCs)].METHODS FIT-interval CRCs observed in a Dutch pilot-program of FIT-based screening were compared to a control group of SD-CRCs in a 1:2 ratio,resulting in 27 FIT-interval CRC and 54 SD-CRCs.Molecular analyses included microsatellite instability(MSI),CpG island methylator phenotype(CIMP),DNA sequence mutations and copy number alterations(CNAs).RESULTS Although no significant differences were reached,FIT-interval CRCs were more often CIMP positive and MSI positive(33%CIMP in FIT-interval CRCs vs 21%in SD-CRCs(P=0.274);19%MSI in FIT-interval CRCs vs 12%in SD-CRCs(P=0.469)),and showed more often serrated pathway associated features such as BRAF(30%vs 12%,P=0.090)and PTEN(15%vs 2.4%,P=0.063)mutations.APC mutations,a classic feature of the adenoma-carcinoma-sequence,were more abundant in SD-CRCs(68%vs 40%in FIT-interval CRCs P=0.035).Regarding CNAs differences between the two groups;FIT-interval CRCs less often showed gains at the regions 8p11.22-q24.3(P=0.009),and more often gains at 20p13-p12.1(P=0.039).CONCLUSION Serrated pathway associated molecular features seem to be more common in FIT-interval CRCs,while classic adenoma carcinoma pathway associated molecular features seem to be more common in SD-CRCs.This indicates that proximal serrated lesions may be overrepresented among FITinterval CRCs.

Climate Change and Its Impact on Ecological Environment in Western Liaoning in Recent 50 years

Based on the observation data of meteorological stations in western Liaoning from 1971 to 2020,the trend,Morlet wavelet,MK mutation and other methods were used to analyze the data.The results show that the annual average temperature of western Liaoning was 9.29℃;the annual average precipitation was 542.2 mm,and the trend change was not obvious;the temperature had obvious quasi-13-year,quasi-19-year and quasi-45-year cycles,and the precipitation had quasi-3-year,quasi-6-year,quasi-14-year and quasi-29-year cycles;there was a sudden change in temperature in 1990,and the warming was significant after the sudden change;the typical abrupt changes of precipitation occurred in 1979 and 2000,but the abrupt changes were not significant.

A Comparative Evaluation of Test Coverage Techniques Effectiveness

Software systems have become complex and challenging to develop and maintain because of the large size of test cases with increased scalability issues. Test case prioritization methods have been successfully utilized in test case management. However, the prohibitively exorbitant cost of large test cases is now the mainstream in the software industry. The growth of agile test-driven development has increased the expectations for software quality. Yet, our knowledge of when to use various path testing criteria for cost-effectiveness is inadequate due to the inherent complexity in software testing. Existing researches attempted to address the issue without effectively tackling the scalability of large test suites to reduce time in regression testing. In order to provide a more accurate way of fault detection in software projects, we introduced novel coverage criteria, called Incremental Cluster-based test case Prioritization (ICP), and investigated its potentials by making a comparative evaluation with three un-clustered traditional coverage-based criteria: Prime-Path Coverage (PPC), Edge-Pair Coverage (EPC) and Edge Coverage (EC) based on mutation analysis. By clustering test suites, based on their dynamic run-time behavior, the number of pair-wise comparisons is reduced significantly. To compare, we analyzed 20 functions from 25 C programs, instrumented faults into the programs, and used the Mull mutation tool to generate mutants and perform a statistical analysis of the results. The experimental results show that ICP can lead to cost-effective improvements in fault detection.

Mutation analysis of PAX6 gene in a large Chinese family with aniridia

Background Mutations in PAX6 gene have been shown to be the genetic cause of aniridia, which is a severe panocular eye disease characterised by iris hypoplasia. However, there is no study to do genetic analysis of aniridia, although there are several case reports in China. Here, we describe a mutation analysis of PAX6 in a large Chinese family with aniridia. Methods Genomic DNA from venous blood samples was prepared. Haplotype analysis was performed with two genetic markers ( D11S904 and D11S935). Fourteen exons of the PAX6 gene were amplified from genomic DNA. Polymerase chain reaction ( PCR) products of each exon were analysed by single strand conformational polymorphism (SSCP). The PCR products having an abnormal pattern were sequenced to confirm the mutation. Results Significant evidence for allele sharing in affected patients was detected suggesting that PAX6 mutation links to aniridia in this family. An extra band corresponding to exon 9 in PAX6 was found by single strand conformational polymorphism analysis in all the aniridia patients in this family, but not detected in the unaffected members. A mutation of C to T was detected by sequencing at the nucleotide 1080 that converts the Arg codon (CGA) to the termination codon (TGA). Conclusions Aniridia is caused by a nonsense mutation of PAX6 gene in the large Chinese kindred. Genetic test is important to prevent the transmission of aniridia to their offsprings in the kindred by prenatal diagnosis.