Patient-centric periodontal research:A pioneering application of patient-reported outcome measures

Conventional dentistry or periodontal research often ignores the human component in favor of clinical outcomes and biological causes.Clinical research is driven by the statistical significance of outcome parameters rather than the satisfaction level of the patient.In this context,patient-centric periodontal research(PCPR)is an approach that considers the patient´s feedback concerning their functional status,experience,clinical outcomes,and accessibility to their treatments.It is argued that data self-reported by the patient might have low reliability owing to the confounding effect of their personal belief,cultural background,and social and economic factors.However,literature has shown that the incorporation of“patient-centric outcome”components considerably enhances the validity and applicability of research findings.Variations in the results of different studies might be due to the use of different and non-standardized assessment tools.To overcome this problem,this editorial enlists various reliable tools available in the literature.In conclusion,we advocate that the focus of researchers should shift from mere periodontal research to PCPR so that the results can be effectively applied in clinical settings and the therapeutic strategy can also change from mere periodontal therapy to patient-centric periodontal therapy.

Analysis on the Translation Methods of the Reported Speech in German Academic Papers-Taking the Translation of“Die Internationalisierung der deutschen Hochschulen”as an Example

Reporting is essential in language use,including the re-expression of other people’s or self’s words,opinions,psychological activities,etc.Grasping the translation methods of reported speech in German academic papers is very important to improve the accuracy of academic paper translation.This study takes the translation of“Internationalization of German Universities”(Die Internationalisierung der deutschen Hochschulen),an academic paper of higher education,as an example to explore the translation methods of reported speech in German academic papers.It is found that the use of word order conversion,part of speech conversion and split translation methods can make the translation more accurate and fluent.This paper helps to grasp the rules and characteristics of the translation of reported speech in German academic papers,and also provides a reference for improving the quality of German-Chinese translation.

HIPPO artificial intelligence:Correlating automated radiographic femoroacetabular measurements with patient-reported outcomes in developmental hip dysplasia

BACKGROUND Hip dysplasia(HD)is characterized by insufficient acetabular coverage of the femoral head,leading to a predisposition for osteoarthritis.While radiographic measurements such as the lateral center edge angle(LCEA)and Tönnis angle are essential in evaluating HD severity,patient-reported outcome measures(PROMs)offer insights into the subjective health impact on patients.AIM To investigate the correlations between machine-learning automated and manual radiographic measurements of HD and PROMs with the hypothesis that artificial intelligence(AI)-generated HD measurements indicating less severe dysplasia correlate with better PROMs.METHODS Retrospective study evaluating 256 hips from 130 HD patients from a hip preservation clinic database.Manual and AI-derived radiographic measurements were collected and PROMs such as the Harris hip score(HHS),international hip outcome tool(iHOT-12),short form(SF)12(SF-12),and Visual Analogue Scale of the European Quality of Life Group survey were correlated using Spearman's rank-order correlation.RESULTS The median patient age was 28.6 years(range 15.7-62.3 years)with 82.3%of patients being women and 17.7%being men.The median interpretation time for manual readers and AI ranged between 4-12 minutes per patient and 31 seconds,respectively.Manual measurements exhibited weak correlations with HHS,including LCEA(r=0.18)and Tönnis angle(r=-0.24).AI-derived metrics showed similar weak correlations,with the most significant being Caput-Collum-Diaphyseal(CCD)with iHOT-12 at r=-0.25(P=0.042)and CCD with SF-12 at r=0.25(P=0.048).Other measured correlations were not significant(P>0.05).CONCLUSION This study suggests AI can aid in HD assessment,but weak PROM correlations highlight their continued importance in predicting subjective health and outcomes,complementing AI-derived measurements in HD management.

A study of reporters as functional entity in news fuzzy language

Fuzziness, as intrinsic property of natural language, appears to be an extremely pervasive phenomenon in language communication with no exception of news reporting. To some extent, the usage of a great number of fuzzy expressions in news reporting reflects the property of reporter as functional entity. On different occasions, reporters, when reporting news, may play such three kinds of roles as the first information source, the second information source or the virtual interpreter. The different roles-playing determines the pragmatic intention of fuzzy language in news reporting.

Saving time and effort:Best practice for adapting existing patientreported outcome measures in hepatology

It is increasingly recognised that collecting patient reported outcome measures(PROMs)data is an important part of healthcare and should be considered alongside traditional clinical assessments.As part of a more holistic view of healthcare provision,there has been an increased drive to implement PROM collection as part of routine clinical care in hepatology.This drive has resulted in an increase in the number of PROMs currently developed to be used in various liver conditions.However,the development and validation of a new PROM is time-consuming and costly.Therefore,before deciding to develop a new PROM,researchers should consider identifying existing PROMs to assess their appropriateness and,if necessary,make adaptations to existing PROMs to ensure their rigour when used with the target population.Little is written in the literature on how to identify and adapt the existing PROMs in hepatology.This article aims to provide a summary of the current literature and guidance regarding identifying and adapting existing PROMs in clinical practice.

Technological developments enable measuring and using patientreported outcomes data in orthopaedic clinical practice

Patient-reported outcomes measures form the backbone of outcomes evaluation in orthopaedics,with most of the literature now relying on these scoring tools to measure change in patient health status.This patient-reported information is increasingly collected routinely by orthopaedic providers but use of the data is typically restricted to academic research.Developments in electronic data capture and the outcome tools themselves now allow use of this data as part of the clinical consultation.This review evaluates the role of patient reported outcomes data as a tool to enhance daily orthopaedic clinical practice,and documents how developments in electronic outcome measures,computer-adaptive questionnaire design and instant graphical display of questionnaire can facilitate enhanced patientclinician shared decision making.

A reporter for noninvasively monitoring gene expression and plant transformation

Reporters have been widely used to visualize gene expression,protein localization,and other cellular activities,but the commonly used reporters require special equipment,expensive chemicals,or invasive treatments.Here,we construct a new reporter RUBY that converts tyrosine to vividly red betalain,which is clearly visible to naked eyes without the need of using special equipment or chemical treatments.We show that RUBY can be used to noninvasively monitor gene expression in plants.Furthermore,we show that RUBY is an effective selection marker for transformation events in both rice and Arabidopsis.The new reporter will be especially useful for monitoring cellular activities in large crop plants such as a fruit tree under field conditions and for observing transformation and gene expression in tissue culture under sterile conditions.

A rapid reporter assay for recombinant human brain natriuretic peptide(rhBNP)by GloSensor technology

Accurate determination of biological activity is essential in quality control of recombinant human brain natriuretic peptide （rhBNP）. In previous study, we successfully developed a genetically modified cell line 293GCAC3-based ELISA assay for rhBNP. But ELISA procedure is still tedious, so this study was aimed to develop a rapid and simple bioassay for rhBNP using GloSensor technology, which provides a platform of flexible luciferase-based biosensors for real-time detection of signaling events in live cells, including cGMP production. A reporter cell line 293GCAGIo-G1 was constructed by transfecting pGloSensorTM 40 F plasmid into 293GCAC3. The reporter assay based on 293GCAGIo-G1 showed high precision with intraassay CV being 8.3% and inter-assay CV being 14.1%; high accuracy with 80%, 100% and 120% recovery rate being 99.2%, 102.4% and 99.0% respectively; and great linearity with R^2 of linear fitting equation being 0.99. Besides, no significant difference was found in test results of reporter assay and 293GCAC3-based ELISA assay （paired t test,p = 0.630）. All these results suggested that the reporter assay was a viable assay for biological determination of rhBNP.

Alpha-fetoprotein-targeted reporter gene expression imaging in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common cancers in Eastern Asia, and its incidence is increasing globally. Numerous experimental models have been developed to better our understanding of the pathogenic mechanism of HCC and to evaluate novel therapeutic approaches. Molecular imaging is a convenient and up-to-date biomedical tool that enables the visualization, characterization and quantification of biologic processes in a living subject. Molecular imaging based on reporter gene expression, in particular, can elucidate tumor-specific events or processes by acquiring images of a reporter gene’s expression driven by tumor-specific enhancers/promoters. In this review, we discuss the advantages and disadvantages of various experimental HCC mouse models and we present in vivo images of tumor-specific reporter gene expression driven by an alpha-fetoprotein (AFP) enhancer/promoter system in a mouse model of HCC. The current mouse models of HCC development are established by xenograft, carcinogen induction and genetic engineering, representing the spectrum of tumor-inducing factors and tumor locations. The imaging analysis approach of reporter genes driven by AFP enhancer/promoter is presented for these different HCC mouse models. Such molecular imaging can provide longitudinal information about carcinogenesis and tumor progression. We expect that clinical application of AFP-targeted reporter gene expression imaging systems will be useful for the detection of AFP-expressing HCC tumors and screening of increased/decreased AFP levels due to disease or drug treatment.

Epidemiological Analysis on Reported Hepatitis C Cases in China from 2012 to 2016

Viral hepatitis is an important challenge to public health worldwide.As hepatitis B is well controlled due to vaccination,the disease burden caused by the spread of hepatitis C has become increasingly prominent.Hepatitis C is an infectious disease that is mainly blood-borne.The rate of chronicity ranges from 55% to 85% after people are infected with the hepatitis C virus （HCV）.

Red fluorescent protein (DsRed2), an ideal reporter for cotton genetic transformation and molecular breeding

Genes encoding reporter proteins are used as visual marker-assisted tools in genetic transformation as well as plant breeding. In this study, the red fluorescent protein identified in Discosoma sp. coral(DsRed2) was successfully used as a visual marker for cotton genetic engineering. DsRed2 was successfully expressed in two cotton cultivars,JIN668 and YZ1, driven by the Ca MV-35 S promoter via the Agrobacterium-mediated transformation. Our results suggest that DsRed2 expression provides an early-stage selection tool for the transgenic calli via visual observation. Red fluorescence can be detected not only in callus and somatic embryos but also in most tissues and organs of mature plants. The transgenic line Yz-2-DsRed2 was crossed with four different cotton cultivars to assess the transgene heritability and stability in different genetic backgrounds.The heritability of the red color was highly stable when Yz-2-DsRed2 was used as a male parent. The DsRed2 gene expressed 100% in the F_1 hybrids. To investigate the relationship between DsRed2 transcription and DNA methylation, a methylation-specific PCR approach was applied to the Ca MV-35 S promoter region. The results showed a negative association between DNA methylation level in the promoter region and the transgene transcription.Taken together, these findings suggest DsRed2 a visual reporter gene for cotton genetic transformation and molecular breeding programs.

Reporter gene systems for the identification and characterization of cancer stem cells

Cancer stem cells(CSCs)are tumor cells that share functional characteristics with normal and embryonic stem cells.CSCs have increased tumor-initiating capacity and metastatic potential and lower sensitivity to chemo-and radiotherapy,with important roles in tumor progression and the response to therapy.Thus,a current goal of cancer research is to eliminate CSCs,necessitating an adequate phenotypic and functional characterization of CSCs.Strategies have been developed to identify,enrich,and track CSCs,many of which distinguish CSCs by evaluating the expression of surface markers,the initiation of specific signaling pathways,and the activation of master transcription factors that control stemness in normal cells.We review and discuss the use of reporter gene systems for identifying CSCs.Reporters that are under the control of aldehyde dehydrogenase 1A1,CD133,Notch,Nanog homeobox,Sex-determining region Y-box 2,and POU class 5 homeobox can be used to identify CSCs in many tumor types,track cells in real time,and screen for drugs.Thus,reporter gene systems,in combination with in vitro and in vivo functional assays,can assess changes in the CSCs pool.We present relevant examples of these systems in the evaluation of experimental CSCs-targeting therapeutics,demonstrating their value in CSCs research.

A High-Performing and Cost-Effective SNP Genotyping Method Using rhPCR and Universal Reporters

We have developed a novel dual enzyme chemistry called rhAmp®SNP genotyping based on RNase H2-dependent PCR (rhPCR) that provides high signal and specificity for SNP analysis. rhAmp SNP genotyping combines a unique two-enzyme system with 3’ end blocked DNA-RNA hybrid primers to interrogate SNP loci. Activation of the blocked primers occurs upon hybridization to its perfectly matched target, which eliminates or greatly reduces primer dimers. A thermostable hot-start RNase H2 cleaves the primer immediately 5’ of the ribose sugar, releasing the blocking group and allowing primer extension. PCR specificity is further improved with the use of a mutant Taq DNA polymerase, resulting in improved allelic discrimination. Signal generation is obtained using a universal reporter system which requires only two reporter probes for any bi-allelic SNP. 1000 randomly selected SNPs were chosen to validate the 95% design rate of the design pipeline. A subsampling of 130 human SNP targets was tested and achieved a 98% call rate, and 99% call accuracy. rhAmp SNP genotyping assays are compatible with various qPCR instruments including QuantStudioTM 7 Flex, CFX384TM, IntelliQube®, and Biomark HDTM. In comparison to TaqMan®, rhAmp SNP genotyping assays show higher signal (Rn) and greater cluster separation, resulting in more reliable SNP genotyping performance. The rhAmp SNP genotyping solution is suited for high-throughput SNP genotyping applications in humans and plants.

Tetracysteine as a Reporter for Gene Therapy

Objective To study the feasibility of using tetracysteine （TC） reporter in gene therapy. Methods Effects of TC reporter and conventional reporter genes encoding green fluorescence protein （GFP） and luciferase （Luc） on expression and function of the therapeutic gene MGMT^P140K were compared. Cytotoxicity and drug resistance were studied by Western blot. TC reporter used in therapy was analyzed by flow cytometry （FCM）. Results The TC reporter had no toxicity to cells and neither affected the expression or activity of therapeutic gene as compared to GFP and Luc. TC could be used in blood sample detection. Conclusion TC is a new kind of reporter gene for lentiviral vector in future gene therapy.

Construction and Identification of the Adenoviral Vector with Dual Reporter Gene for Multimodality Molecular Imaging

Summary： In this study, the recombinant adenovirus （Ad） vector containing dual reporter gene [i.e. human transferrin receptor gene （TFRC） and firefly luciferase reporter gene] was constructed to provide a novel experimental tool for magnetic resonance （MR） and bioluminescence dual-modality molecular imaging. The cDNA of TFRC was amplified by polymerase chain reaction （PCR） and cloned into the multiple cloning site of pShuttle-CMV-CMV-Luciferase vector. After identification by Sfi I digestion and sequencing, pShuttle-TFRC-Luciferase vector and the adenoviral backbone vector （pAdeno） were subjected to homologous recombination. The correct recombinant plasmid was then transfected into 293 packaging cells to produce adenoviral particles and confirmed by PCR. After infection of human colo- rectal cancer LOVO cells with Ad-TFRC-Luciferase, the expressions of transferrin receptor （TfR） and luciferase protein were detected respectively by Western blotting and bioluminescence imaging in vitro. The results showed that TFRC gene was successfully inserted into the adenoviral shuttle vector carrying luciferase gene. DNA sequence analysis indicated that the TFRC gene sequence in the shuttle plasmid was exactly the same as that reported in GenBank. The recombinant plasmid was identified correct by restriction digestion. Ad-TFRC-Luciferase recombinant adenovirns was constructed successfully, and the virus titer was 1.6x10^10 pfu/mL. Forty-eight h after dual reporter gene transfection, the expressions of TfR and luciferase protein were increased significantly （P〈0.01）. It was concluded that the recombinant adenovirus vector with dual reporter gene was successfully established, which may be used for in vivo tracing target cells in multimodality imaging.

Duplex micro RNAs assay based on target-triggered universal reporter hybridization

In this paper, we designed and evaluated a duplex detection strategy for micro RNAs（mi RNAs） using universal probe-based target-triggered double hybridization and fluorescent microsphere-based assay system（x MAP array）. In the absence of target mi RNA, reporter DNA cannot hybridize stably with the immobilized capture DNA due to its low melting temperature. Only after adding target mi RNA, can reporter probe hybridize with capture probe to form a stable three-component complex. This targettriggered stable hybridization makes this method possible for highly selective and sensitive detection of multiple mi RNAs. We exemplified a quantitative detection of duplex mi RNAs with a limit of detection of40 p M. The x MAP array platform holds the potential of extending this approach to simultaneous detection of up to 100 mi RNA targets. Considering the simplicity, rapidity and multiplexing, this work promised a potential detection of multiple mi RNA biomarkers for early disease diagnosis and prognosis.

Synthesis and characterization of reporter molecules embedded core-shell nanoparticles as SERS nanotags

Surface-enhanced Raman scattering(SERS)spectroscopy is presented as a sensitive and spe-cific molecular tool for clinical diagnosis and prognosis monitoring of various diseases including cancer.In order for clinical application of SERS technique,an ideal method of bulk synthesis of SERS nanoparticles is necessary to obtain sensitive,stable and highly reproducible Raman signals.In this contribution,we determined the ideal conditions for bulk synthesis of Raman reporter(Ra)molecules embedded silver-gold core-shell nanoparticles(Au@Ra@AgNPs)using hydroquinone as reducing agent of silver nitrate.By using UV-Vis spectroscopy,Raman spectroscopy and transmission electron microscopy(TEM),we found that a 2∶1 ratio of silver nitrate to hydroquinone is ideal for a uniform silver coating with a strong and stable Raman signal.Through stability testing of the optimized Au@Ra@AgNPs over a two-week period,these SERS nanotags were found to be stable with minimal signal change occurred.The sta-bility of antibody linked SERS nanotags is also crucial for cancer and disease diagnosis,thus,we further conjugated the as-prepared SERS nanotags with anti-EpCAM antibody,in which the stability of bioconjugated SERS nanotags was tested over eight days.Both UV-Vis and SERS spectroscopy showed stable absorption and Raman signals on the anti-EpCAM conju-gated SERS nanotags,indicating the great potential of the synthesized SERS nanotags for future applications which require large,reproducible and uniform quantities in order for cancer biomarker diagnosis and monitoring.

Fish Consumption Advisories and the Surprising Relationship to Prevalence Rate of Developmental Disability as Reported by Public Schools

According to the Environmental Protection Agency (EPA), fish consumption is the most significant route of mercury exposure, and the concern is greatest for women of childbearing age due to the potential for neurodevelopmental effects on a developing fetus. Rates of developmental disorders vary. But in 2008 it was demonstrated that the rate of autism is higher near industries that emit heavy metals. Furthermore past research findings can be taken to show that where a pregnancy occurred may predict later autism likelihood in the offspring more than where diagnosis occurs. If mercury plays any role in developmental disabilities, the rate of disability should relate to any reliable direct measure of contamination. The current research focuses on one index of environmental mercury contamination. Specifically, mercury-related fish advisories are found to be a surprisingly strong predictor of a state’s autism rate, r = 0.48, p < 0.001. The relationship remains strong after controlling for student to teacher ratio and per pupil spending. It is argued that a secular increase in autism has been occurring and that prenatal exposure to heavy metal toxins may play a significant role. Because we suspect this finding may be of some interest, the full data set is provided in the appendix so that researchers can independently analyze the key findings which rely on CDC, EPA and IDEA data sets.

Pedestrian Mortality between 2006 and 2010 in China: Findings from Non-police Reported Data

Pedestrian safety in China is an important but largely neglected issue, in part due to the substantial under-reporting within police data. In this study we aimed to examine changes in pedestrian fatality between 2006 and 2010 in China using non-police reported data. A multi-year study was conducted based on the mortality data during 2006-2010 from the Disease Surveillance Points （DSP） data in China. Between 2006 and 2010, the crude pedestrian mortality increased from 7.0 to 10.5 per 100 000 populations. Annual pedestrian mortality from DSP data was 13 times in 2006 and 55 times in 2010 mortality for pedestrians and passengers from police-reported data in the corresponding years. After controlling for sex, age,

Improved patient reported outcomes with functional articulating spacers in two-stage revision of the infected hip

BACKGROUND Two-stage revision arthroplasty with an antibiotic-loaded spacer is the treatment of choice in chronically infected total hip arthroplasties.Interval spacers can be functional articulating or prefabricated.Functional results of these spacers have scarcely been reported.AIM To compare retrospectively the patient reported outcome and infection eradication rate after two-stage revision arthroplasty of the hip with the use of a functional articulating or prefabricated spacer.METHODS All patients with two-stage revision of a hip prosthesis at our hospital between 2003 and 2016 were included in this retrospective cohort study.Patients were divided into two groups;patients treated with a functional articulating spacer or with a prefabricated spacer.Patients completed the Hip Osteoarthritis Outcome Score and the EQ-5D-3L(EQ-5D)and the EQ-5D quality of life thermometer(EQVAS)scores.Primary outcomes were patient reported outcome and infection eradication after two-stage revision.The results of both groups were compared to the patient acceptable symptom state for primary arthroplasty of the hip.Secondary outcomes were complications during spacer treatment and at final follow-up.Descriptive statistics,mean and range are used to represent the demographics of the patients.For numerical variables,students’t-tests were used to assess the level of significance for differences between the groups,with 95%confidence intervals;for binary outcome,we used Fisher’s exact test.RESULTS We consecutively treated 55 patients with a prefabricated spacer and 15 patients with a functional articulating spacer of the hip.The infection eradication rates for functional articulating and prefabricated spacers were 93%and 78%,respectively(P>0.05).With respect to the functional outcome,the Hip Osteoarthritis Outcome Score(HOOS)and its subscores(all P<0.01),the EQ-5D(P<0.01)and the EQVAS scores(P<0.05)were all significantly better for patients successfully treated with a functional articulating spacer.More patients in the functional articulating spacer group reached the patient acceptable symptom state for the HOOS pain,HOOS quality of life and EQ-VAS.The number of patients with a spacer dislocation was not significantly different for the functional articulating or prefabricated spacer group(P>0.05).However,the number of dislocations per patient experiencing a dislocation was significantly higher for patients with a prefabricated spacer(P<0.01).CONCLUSION Functional articulating spacers lead to improved patient reported functional outcome and less perioperative complications after two-stage revision arthroplasty of an infected total hip prosthesis,while maintaining a similar infection eradication rate compared to prefabricated spacers.