Evaluation of Sensitivities and Specificities of SARS-CoV Detection by Real-time Quantitative Reverse Transcription-PCR Assays

The etiological agent of severe acute respiratory syndrome(SARS) was identified as a new coronavirus,termed SARS-CoV. Establishment of an efficient and sensitive diagnostic system of SARS-CoV genetic materials is crucial for SARS control. In this study,we quantified SARS-CoV mRNAs in both infected cell culture lysate and in supernatant by using Real-time quantitative revere transcription-PCR based on EvaGreenTM dye and Taqman-MGB probes. For extensive evaluation of sensitivities and specificities,13 pairs of primers and 4 probes were designed based on different genes of SARS-CoV. Glyceraldehydes-3-phosphate dehydrogenase(GAPDH) was selected as the internal control gene. Results showed that S-gene-specific PCR was the most sensitive for detection,but because of its sequence variability in the different viral strains,primers and a probe based on the N gene were suitable substitutions. Meanwhile,we found the mRNA concentrations in cell culture lysates were much higher than in cell supernatant and facilited more sensitive detection of the SARS-CoV.

Specificities of the Local Data and Interactive Visualization

The objective is to know and to exploit specificities of the local data because Madagascar needs to the media economic surveys deepened on its cultural and social diversities. The problems remain on the facts that the journalists are exceeded by the events and are often constrained to be unaware of the environment of proximity--policies, societies, and economics which could become inexhaustible sources. In this case, how and up to what point will they manage to collect all the data related there, to exploit them and to place them at the disposal of the public？ We chose a methodology of investigation according to the research methods developed for the study of the industrial and agricultural systems （Bear, Gibbon, Haggblade, ＆ Ritchie, 1993; Boomgard, Davies, Haggblade, ＆ Mead, 1992; Laurent, 1993; Montigaud, 1992） in order to establish the cartography of the media, the actors, the sets of themes to the menu. This enabled us to raise a whole proliferation of the media. The lnternet has also been diffused since 1997.

A novel saliva-based miRNA profile to diagnose and predict oral cancer

Oral cancer (OC) is the most common form of head and neck cancer. Despite the high incidence and unfavourable patient outcomes, currently, there are no biomarkers for the early detection of OC. This study aims to discover, develop, and validate a novel saliva-based microRNA signature for early diagnosis and prediction of OC risk in oral potentially malignant disorders (OPMD).The Cancer Genome Atlas (TCGA) miRNA sequencing data and small RNA sequencing data of saliva samples were used to discover differentially expressed miRNAs. Identified miRNAs were validated in saliva samples of OC (n=50), OPMD (n=52), and controls(n=60) using quantitative real-time PCR. Eight differentially expressed miRNAs (miR-7-5p, miR-10b-5p, miR-182-5p, miR-215-5p,miR-431-5p, miR-486-3p, miR-3614-5p, and miR-4707-3p) were identified in the discovery phase and were validated. The efficiency of our eight-miRNA signature to discriminate OC and controls was:area under curve (AUC):0.954, sensitivity:86%, specificity:90%,positive predictive value (PPV):87.8%and negative predictive value (NPV):88.5%whereas between OC and OPMD was:AUC:0.911,sensitivity:90%, specificity:82.7%, PPV:74.2%and NPV:89.6%. We have developed a risk probability score to predict the presence or risk of OC in OPMD patients. We established a salivary miRNA signature that can aid in diagnosing and predicting OC,revolutionising the management of patients with OPMD. Together, our results shed new light on the management of OC by salivary miRNAs to the clinical utility of using miRNAs derived from saliva samples.

Durable K-ion batteries with 100% capacity retention up to 40,000 cycles

Currently,the major challenge in terms of research on K-ion batteries is to ensure that they possess satisfactory cycle stability and specific capacity,especially in terms of the intrinsically sluggish kinetics induced by the large radius of K+ions.Here,we explore high-performance K-ion half/full batteries with high rate capability,high specific capacity,and extremely durable cycle stability based on carbon nanosheets with tailored N dopants,which can alleviate the change of volume,increase electronic conductivity,and enhance the K+ion adsorption.The as-assembled K-ion half-batteries show an excellent rate capability of 468 mA h g^(−1) at 100 mA g^(−1),which is superior to those of most carbon materials reported to date.Moreover,the as-assembled half-cells have an outstanding life span,running 40,000 cycles over 8 months with a specific capacity retention of 100%at a high current density of 2000 mA g^(−1),and the target full cells deliver a high reversible specific capacity of 146 mA h g^(−1) after 2000 cycles over 2 months,with a specific capacity retention of 113%at a high current density of 500 mA g^(−1),both of which are state of the art in the field of K-ion batteries.This study might provide some insights into and potential avenues for exploration of advanced K-ion batteries with durable stability for practical applications.

Upregulated lncRNA PRNT promotes progression and oxaliplatin resistance of colorectal cancer cells by regulating HIPK2 transcription

BACKGROUND Colorectal cancer(CRC)is the third most common cancer and a significant cause of cancer-related mortality globally.Resistance to chemotherapy,especially during CRC treatment,leads to reduced effectiveness of drugs and poor patient outcomes.Long noncoding RNAs(lncRNAs)have been implicated in various pathophysiological processes of tumor cells,including chemotherapy resistance,yet the roles of many lncRNAs in CRC remain unclear.AIM To identify and analyze the lncRNAs involved in oxaliplatin resistance in CRC and to understand the underlying molecular mechanisms influencing this resistance.METHODS Gene Expression Omnibus datasets GSE42387 and GSE30011 were reanalyzed to identify lncRNAs and mRNAs associated with oxaliplatin resistance.Various bioinformatics tools were employed to elucidate molecular mechanisms.The expression levels of lncRNAs and mRNAs were assessed via quantitative reverse transcription-polymerase chain reaction.Functional assays,including MTT,wound healing,and Transwell,were conducted to investigate the functional implications of lncRNA alterations.Interactions between lncRNAs and trans-cription factors were examined using RIP and luciferase reporter assays,while Western blotting was used to confirm downstream pathways.Additionally,a xenograft mouse model was utilized to study the in vivo effects of lncRNAs on chemotherapy resistance.RESULTS LncRNA prion protein testis specific(PRNT)was found to be upregulated in oxaliplatin-resistant CRC cell lines and negatively correlated with homeodomain interacting protein kinase 2(HIPK2)expression.PRNT was demonstrated to sponge transcription factor zinc finger protein 184(ZNF184),which in turn could regulate HIPK2 expression.Altered expression of PRNT influenced CRC cell sensitivity to oxaliplatin,with overexpression leading to decreased sensitivity and decreased expression reducing resistance.Both RIP and luciferase reporter assays indicated that ZNF184 and HIPK2 are targets of PRNT.The PRNT/ZNF184/HIPK2 axis was implicated in promoting CRC progression and oxaliplatin resistance both in vitro and in vivo.CONCLUSION The study concludes that PRNT is upregulated in oxaliplatin-resistant CRC cells and modulates the expression of HIPK2 by sponging ZNF184.This regulatory mechanism enhances CRC progression and resistance to oxaliplatin,positioning PRNT as a promising therapeutic target for CRC patients undergoing oxaliplatin-based chemotherapy.

Transcriptional regulation in the development and dysfunction of neocortical projection neurons

Glutamatergic projection neurons generate sophisticated excitatory circuits to integrate and transmit information among different cortical areas,and between the neocortex and other regions of the brain and spinal cord.Appropriate development of cortical projection neurons is regulated by certain essential events such as neural fate determination,proliferation,specification,differentiation,migration,survival,axonogenesis,and synaptogenesis.These processes are precisely regulated in a tempo-spatial manner by intrinsic factors,extrinsic signals,and neural activities.The generation of correct subtypes and precise connections of projection neurons is imperative not only to support the basic cortical functions(such as sensory information integration,motor coordination,and cognition)but also to prevent the onset and progression of neurodevelopmental disorders(such as intellectual disability,autism spectrum disorders,anxiety,and depression).This review mainly focuses on the recent progress of transcriptional regulations on the development and diversity of neocortical projection neurons and the clinical relevance of the failure of transcriptional modulations.

Magnetic and electrical transport properties in GdAlSi and SmAlGe

We conduct a detailed examination of the magnetic and electrical transport properties in GdAlSi and SmAlGe crystals,which possess a LaPtSi-type structure(space group I4_(1)md).The magnetic susceptibility data unambiguously reveal magnetic ordering below a characteristic transition temperature(T_(N)).For GdAlSi,a hysteresis loop is observed in the magnetization and magnetoresistance curves within the ab plane when the magnetic field is applied below T_(N),which is around32 K.Notable specific heat anomalies are detected at 32 K for GdAlSi and 6 K for SmAlGe,confirming the occurrence of magnetic transitions.In addition,the extracted magnetic entropy at high temperatures is consistent with the theoretical value of Rln(2J+1) for J=7/2 in Gd^(3+) and J=5/2 in Sm^(3+),respectively.SmAlGe also exhibits Schottky-like specific heat contributions.Additionally,both GdAlSi and SmAlGe exhibit positive magnetoresistance and a normal Hall effect.

Review of the SiC LDMOS power device

Silicon carbide(SiC),as a third-generation semiconductor material,possesses exceptional material properties that significantly enhance the performance of power devices.The SiC lateral double-diffused metal–oxide–semiconductor(LDMOS)power devices have undergone continuous optimization,resulting in an increase in breakdown voltage(BV)and ultra-low specific on-resistance(Ron,sp).This paper has summarized the structural optimizations and experimental progress of SiC LDMOS power devices,including the trench-gate technology,reduced surface field(RESURF)technology,doping technology,junction termination techniques and so on.The paper is aimed at enhancing the understanding of the operational mechanisms and providing guidelines for the further development of SiC LDMOS power devices.

Gamma oscillations and their role in orchestrating balance and communication following stroke

Induced brain oscillations in the gamma range have recently garnered attention due to their reported neuroprotective effects in the treatment of Alzheimer’s disease.This method differs from pharmacological approaches by tapping into the neuronal population dynamics that underlie the homeostatic processes in the brain that are crucial for the recovery of function.Recently,induced gamma-range oscillations have been used to improve cerebral blood flow,motor function,and synaptic plasticity in a mouse model of focal stroke,highlighting the broad potential of recruiting intrinsic recovery processes for the treatment of neurological conditions.Addressing open questions,such as the frequency specificity of the benefits,will shed light on the intrinsic processes involved and allow clinicians to optimize recovery after stroke.

Linear magnetoresistance and structural distortion in layered SrCu_(4-x)P_(2) single crystals

We report a systematic study on layered metal SrCu_(4-x)P_(2) single crystals via transport, magnetization, thermodynamic measurements and structural characterization. We find that the crystals show large linear magnetoresistance without any sign of saturation with a magnetic field up to 30T. We also observe a phase transition with significant anomalies in resistivity and heat capacity at T_(p)~140 K. Thermal expansion measurement reveals a subtle lattice parameter variation near Tp, i.e.,?L_(c)/L_(c)~0.062%. The structural characterization confines that there is no structure transition below and above T_(p). All these results suggest that the nonmagnetic transition of SrCu_(4-x)P_(2) could be associated with structural distortion.

Accurate diagnosis of severe coronary stenosis based on resting magnetocardiography: a prospective, single-center, cross-sectional analysis

OBJECTIVE To evalu ate the role of resting magnetocardiography in identifying seve re coronary artery stenosis in patients with suspected coronary artery disease.METHODS A total of 513 patients with angina symptoms were included and divided into two groups based on the extent of coronary artery disease determined by angiography:the non-severe coronary stenusis group(<70% stenosis) and the severe coronary stenosis group(≥70% stenosis).The diagnostic model was constructed using magnetic field map(MFM) parameters,either individually or in combination with clinical indicators.The performance of the models was evaluated using receiver operating characteristic curves,accuracy,sensitivity,specificity,positive predictive value(PPV) and ne gative predictive value(NPV).Calibration plots and decision curve analysis were performed to investigate the clinical utility and performance of the models,respectively.RESULTS In the severe coronary stenosis group,QR_MCTDd,S_MDp,and TT_(MA)C_(50) were significantly higher than those in the non-severe coronary stenosis group(10,46±10.66 vs,5.11±6.07,P <0.001;7.2±8.64 vs.4.68±6.95,P=0.003;0.32±57.29 vs.0.26±57.29,P <0.001).While,QR_MV_(amp),R_(MA),and T_(MA) in the severe coronary stenosis group were lower(0.23±0.16 vs.0.28±0.16,P<0.001;55.06±48.68 vs.59.24±53.01,P<0.001;51.67±39.32 vs. 60.45±51.33,P <0.001).Seven MFM parameters were integrated into the model,resulting in an area under the curve of 0.810(95% CI:0.765-0.855).The sensitivity,specificity,PPV,NPV,and accurecy were 71.7%,80.4%,93.3%,42.8 %,and 73.5%;respectevely.The combined model exhibited an area under the curve of 0.845(95% CI:0.798-0.892).The sensitivity,specificity,PPV,NPV,and accuracy were 84.3%,73.8%,92.6%,54.6%,and 82.1%;respectively.Calibration curves demonstrate d excellent agreement between the nomogram prediction and actual observation.The decision curve analysis showed that the c ombine d model provided greater net benefit compared to the magnetocardingraphy model.CONCLUSIONS The novel quantitative MFM parameters,whether used individually or in combination with clinical indicators,have been shown to effectively pre dict the risk of severe coronary stenosis in patients presenting with angina-like symptoms.Magnetocardiography,an emerging non-invasive diagnostic tool,warrants further exploration for its potential in diagnosing coronary heart disease.

Optimality of Group Testing with Differential Misclassification

Group testing is a method that can be used to estimate the prevalence of rare infectious diseases,which can effectively save time and reduce costs compared to the method of random sampling.However,previous literature only demonstrated the optimality of group testing strategy while estimating prevalence under some strong assumptions.This article weakens the assumption of misclassification rate in the previous literature,considers the misclassification rate of the infected samples as a differentiable function of the pool size,and explores some optimal properties of group testing for estimating prevalence in the presence of differential misclassification conforming to this assumption.This article theoretically demonstrates that the group testing strategy performs better than the sample by sample procedure in estimating disease prevalence when the total number of sample pools is given or the size of the test population is determined.Numerical simulation experiments were conducted to evaluate the performance of group tests in estimating prevalence in the presence of dilution effect.

A comparison of model choice strategies for logistic regression

Purpose:The purpose of this study is to develop and compare model choice strategies in context of logistic regression.Model choice means the choice of the covariates to be included in the model.Design/methodology/approach:The study is based on Monte Carlo simulations.The methods are compared in terms of three measures of accuracy:specificity and two kinds of sensitivity.A loss function combining sensitivity and specificity is introduced and used for a final comparison.Findings:The choice of method depends on how much the users emphasize sensitivity against specificity.It also depends on the sample size.For a typical logistic regression setting with a moderate sample size and a small to moderate effect size,either BIC,BICc or Lasso seems to be optimal.Research limitations:Numerical simulations cannot cover the whole range of data-generating processes occurring with real-world data.Thus,more simulations are needed.Practical implications:Researchers can refer to these results if they believe that their data-generating process is somewhat similar to some of the scenarios presented in this paper.Alternatively,they could run their own simulations and calculate the loss function.Originality/value:This is a systematic comparison of model choice algorithms and heuristics in context of logistic regression.The distinction between two types of sensitivity and a comparison based on a loss function are methodological novelties.

Karyotype establishment and development of specific molecular markers of Aegilops geniculata Roth based on SLAF-seq

The constant evolution of pathogens poses a threat to wheat resistance against diseases,endangering food security.Developing resistant wheat varieties is the most practical approach for circumventing this problem.As a close relative of wheat,Aegilops geniculata,particularly accession SY159,has evolved numerous beneficial traits that could be applied to improve wheat.In this study,we established the karyotype of SY159 by fluorescence in situ hybridization(FISH)using the oligonucleotide probes Oligo-pTa535 and Oligo-pSc119.2 and a complete set of wheat–Ae.geniculata accession TA2899 addition lines as a reference.Using specific-locus amplified fragment sequencing(SLAF-seq)technology,400 specific markers were established for detecting the SY159 chromosomes with efficiencies reaching 81.5%.The SY159-specific markers were used to classify the different homologous groups of SY159 against the wheat-Ae.geniculata addition lines.We used these specific markers on the 7Mg chromosome after classification,and successfully confirmed their suitability for studying the different chromosomes of SY159.This study provides a foundation for accelerating the application of SY159 in genetic breeding programs designed to improve wheat.

Comparative utility of vestibular function tests in patients with peripheral and central vestibular dysfunction

Background: Bithermal caloric irrigation, video head impulse test(vHIT), and rotational testing are commonly used to assess peripheral vestibular function, but the relative clinical utility of each test in differentiating patients with peripheral vestibulopathy is debated.Objectives: To determine whether(1) the combination of two or more vestibular tests enhances diagnostic utility over a single test;(2) abnormal test results on vestibular tests correlate with one another.Methods: Retrospective analysis of data collected from multidisciplinary vestibular clinics at two academic medical centers from 2016 to 2022.Results: 150 patients(54.10 ± 15.09 years, 88 females) were included. No individual test was significantly better at predicting the presence of peripheral vestibular damage(p > 0.05). vHIT test results improved significantly when combined with either the caloric test(p = 0.007) or rotary chair test(p = 0.039). Caloric and rotational testing had high sensitivity(74.65% and 76.06%, respectively) and specificity(83.54% and 78.48%, respectively). vHIT demonstrated excellent specificity(89.87%) but poor sensitivity(47.89%). Caloric, vHIT, and rotary chair tests results did not correlate with one another(p > 0.05).Conclusions: Vestibular function tests have comparable diagnostic utility, yet each offers unique advantages. Caloric and rotational testing may be best suited for screening peripheral damage and vHIT may function ideally as a confirmatory test.

Energy dissipation mechanism and ballistic characteristic optimization in foam sandwich panels against spherical projectile impact

This study systematically examines the energy dissipation mechanisms and ballistic characteristics of foam sandwich panels(FSP)under high-velocity impact using the explicit non-linear finite element method.Based on the geometric topology of the FSP system,three FSP configurations with the same areal density are derived,namely multi-layer,gradient core and asymmetric face sheet,and three key structural parameters are identified:core thickness(t_(c)),face sheet thickness(t_(f))and overlap face/core number(n_(o)).The ballistic performance of the FSP system is comprehensively evaluated in terms of the ballistic limit velocity(BLV),deformation modes,energy dissipation mechanism,and specific penetration energy(SPE).The results show that the FSP system exhibits a significant configuration dependence,whose ballistic performance ranking is:asymmetric face sheet>gradient core>multi-layer.The mass distribution of the top and bottom face sheets plays a critical role in the ballistic resistance of the FSP system.Both BLV and SPE increase with tf,while the raising tcor noleads to an increase in BLV but a decrease in SPE.Further,a face-core synchronous enhancement mechanism is discovered by the energy dissipation analysis,based on which the ballistic optimization procedure is also conducted and a design chart is established.This study shed light on the anti-penetration mechanism of the FSP system and might provide a theoretical basis for its engineering application.

Experimental Study on the Chloride Ion Concentration of Cement Pastes Prepared with Limestone Powder

To investigate the impact of limestone powder on the chloride ion concentration coefficient of cement pastes,various techniques such as scanning electron microscopy(SEM),X-ray diffraction(XRD),thermogravimetric analysis(TGA),and mercury-porosimetry(MIP)were employed in this paper.The findings demonstrate that the creation of Friedel's salt is inversely associated with the addition of limestone powder,that is,Friedel's salt production is lessened by adding more limestone powder,however,the coefficient of chloride ion concentration initially decreased and then increased again,as does the porosity,and most likely the pore size as well.The specific surface area of limestone powder has increased,and the content of Friedel’s salt increased first and then decreased.However,the shifting trend of Friedel's salt and chloride ion concentration coefficient is in direct opposition,and the pore structure was therefore significantly enhanced.The results of this study offer robust theoretical backing for the inclusion of limestone powder in concrete and provide a positive assessment of its potential applications.

Influence of B4C and ZrB2 reinforcements on microstructural,mechanical and wear behaviour of AA 2014 aluminium matrix hybrid composites

Considering their affordability and high strength-to-weight ratio,lightweight aluminium alloys are the subject of intensive research aimed at improving their properties for use in the aerospace industry.This research effort aims to develop novel hybrid composites based on AA 2014 alloy through the use of liquid metallurgy stir casting to reinforce dual ceramic particles of Zirconium Diboride(ZrB_(2))and Boron Carbide(B4C).The weight percentage(wt%)of ZrB_(2) was varied(0,5,10,and 15),while a constant 5 wt%of B4C was maintained during this fabrication.The as-cast samples have been assessed using an Optical Microscope(OM)and a Scanning Electron Microscope(SEM)with Energy Dispersive Spectroscopy(EDS).The properties such as hardness,tensile strength,and wear characteristics of stir cast specimens were assessed to examine the impact of varying weight percentages of reinforcements in AA 2014 alloy.In particular,dry sliding wear behaviour was evaluated considering varied loads using a pin-on-disc tribotester.As the weight%of ZrB_(2) grew and B4C was incorporated,hybrid composites showed higher hardness,tensile strength,and wear resistance.Notably,the incorporation of a cumulative reinforcement consisting of 15 wt%ZrB_(2) and 5 wt%B4C resulted in a significant 31.86%increase in hardness and a 44.1%increase in tensile strength compared to AA 2014 alloy.In addition,it has been detected that wear resistance of hybrid composite pin(containing 20 wt%cumulative reinforcement)is higher than that of other stir cast wear test pins during the whole range of applied loads.Fractured surfaces of tensile specimens showed ductile fracture in the AA 2014 matrix and mixed mode for hybrid composites.Worn surfaces obtained employing higher applied load indicated abrasive wear with little plastic deformation for hybrid composites and dominant adhesive wear for matrix alloy.Hence,the superior mechanical and tribological performance of hybrid composites can be attributed to dual reinforcement particles being dispersed well and the effective transmission of load at this specific composition.

Basic regulatory science behind drug substance and drug product specifications of monoclonal antibodies and other protein therapeutics

In this review,we focus on providing basics and examples for each component of the protein therapeutic specifications to interested pharmacists and biopharmaceutical scientists with a goal to strengthen understanding in regulatory science and compliance.Pharmaceutical specifications comprise a list of important quality attributes for testing,references to use for test procedures,and appropriate acceptance criteria for the tests,and they are set up to ensure that when a drug product is administered to a patient,its intended therapeutic benefits and safety can be rendered appropriately.Conformance of drug substance or drug product to the specifications is achieved by testing an article according to the listed tests and analytical methods and obtaining test results that meet the acceptance criteria.Quality attributes are chosen to be tested based on their quality risk,and consideration should be given to the merit of the analytical methods which are associated with the acceptance criteria of the specifications.Acceptance criteria are set forth primarily based on efficacy and safety profiles,with an increasing attention noted for patient-centric specifications.Discussed in this work are related guidelines that support the biopharmaceutical specification setting,how to set the acceptance criteria,and examples of the quality attributes and the analytical methods from 60 articles and 23 pharmacopeial monographs.Outlooks are also explored on process analytical technologies and other orthogonal tools which are on-trend in biopharmaceutical characterization and quality control.

Old-growth mixed dipterocarp forests show variable losses and gains in aboveground biomass and standing carbon over forty years

Background:No studies have documented long-term trends in aboveground biomass(AGB)for mixed-dipterocarp forests(MDF),the dominant rain forest type in tropical wet equatorial Asia.In our study,we sought to document such trends over forty years across three sites representing lowland to lower montane elevations.Methods:To do this,we established fifty 100 m×25 m plots in 1978 across three sites sampled along an elevation gradient,identified as mature old-growth forest.We measured trees for diameter at breast height that we identified to species and tagged.We took wood samples to calculate species wood-specific gravity.We re-measured plots in 1998 and again in 2018.Results:We show standing AGB for all sites combined to be 517.52 Mg·ha^(-1)in 1978,but this declined by 17%over 40 years to 430.11 Mg·ha^(-1).No differences exist among sites in AGB primarily because of considerable within site variation;but interactions of time with site show declines across sites were not uniform,one remained about the same.Relatively few species represented a high proportion of the AGB with the top five species comprising between 34%and 65%,depending upon site and year sampled.One species,Mesua nagassarium,represented a disproportionately large amount of AGB and decline over time,particularly at the low elevation site.Conclusions:Our results are directly relevant to estimating AGB and standing carbon sequestered in MDF.Our study is the first to demonstrate varying but overall,declining trends in amounts of AGB among forests making predictions of biomass and standing carbon in MDF difficult over wide regions.