Change in clinical parameters after subgingival instrumentation for the treatment of periodontitis and timing of periodontal re-evaluation: A systematic review and meta-analysis.

AIM: To evaluate the changes in periodontal parameters (reduction in probing pocket depth [PPD], gain in clinical attachment level [CAL] and reduction in full-mouth bleeding on probing [BoP]) after subgingival instrumentation of periodontal pockets at different time points in systemically healthy patients suffering from periodontitis. MATERIALS AND METHODS: Four databases were searched for RCTs that carried out subgingival instrumentation in periodontal pockets and evaluated PPD at a minimum of two consecutive time points other than baseline. The analysis was conducted for both all pocket depths and stratified for initially shallow (4-5 mm) and deep (≥6 mm) pockets and data were extracted for various time points, 1-2, 3-4 and 5-6 months. Weighted mean effects (WMEs) were calculated with 95% confidence interval (CI) and predictive intervals were calculated. RESULTS: Twenty-nine RCTs were identified, and all of them were included in the meta-analysis. The results showed that for both shallow and deep pockets there was a small though clinically meaningful change between 1- to 2-month and 3- to 4-month time points and between these and 5-6 months. CONCLUSIONS: In systemically healthy patients, the greater part of reduction in PPD and gain in CAL occurs within the first 1-2 months after subgingival instrumentation. However, additional benefits in terms of pocket depth reduction occur beyond these early time points.

Re-evaluation of the reduced heart weights in male rats in a 28-day oral repeated-dose toxicity study of tetramethylammonium hydroxide.

We recently conducted a detailed hazard assessment of tetramethylammonium hydroxide (TMAH), a priority chemical substance under the Japan Chemical Substances Control Law. During this assessment, there was debate regarding the reduced heart weight observed in the treated male groups in the 28-day rat oral repeated-dose toxicity study. This finding was not observed in females in this study and in both sexes of oral toxicity studies for tetramethylammonium chloride (TMAC) or tetramethylammonium hydrogen phthalate (TMAHP). Unpublished individual data from the oral TMAH developmental and reproductive toxicity (DART) screening study were also obtained; no effect on heart weight was observed. In addition, background data on rat heart weight from six 28-day oral toxicity studies conducted in the same facility, year, strain, age, and breeder as the TMAH study were obtained from the Japan Existing Chemical Substances Database (JECDB). These investigations suggest that the statistically significant lower heart weight in the treated males in the 28-day toxicity study is likely caused by an incidental skewing of individuals with heavier heart weights toward control male groups and is not due to TMAH treatment. Thus, it is worthwhile to include as much relevant data as possible to confirm or refute unexpected findings in toxicity studies.

A retrospective evaluation of SwePEWS use in paediatric patients with COVID-19 and RSV infection.

AIM: As early detection of deterioration is a challenge in children, the Swedish Paediatric Early Warning Score (SwePEWS) is used to systematically assess paediatric patients' clinical state. Here, we aimed to evaluate the use and predictive ability of SwePEWS. METHODS: Electronic health records of paediatric patients admitted due to respiratory syncytial virus infection or COVID-19 were reviewed retrospectively. Registered vital signs were compared to the assigned SwePEWS score and monitored vital sign values to identify discrepancies. Additionally, SwePEWS's ability to predict transfer to the paediatric intensive care unit (PICU) was assessed. RESULTS: Among 1374 SwePEWS assessments, one-third were either incomplete or contained errors. Incomplete SwePEWS assessments were more frequent during night-time. Single measurements of oxygen saturation presented lower values compared to average saturation from continuous monitoring. SwePEWS's ability to predict PICU transfer was low. CONCLUSION: There was a surprisingly high occurrence of underestimated SwePEWS scores. This study provides new insights into pitfalls when developing and implementing paediatric early warning scores for systematic re-evaluations in paediatric patients.

Acupuncture for Low Back Pain: Reevaluation of Systematic Reviews and Meta-analyses.

PURPOSE OF REVIEW: This overview aims to reevaluate the methodological quality, report quality, and evidence quality of systematic reviews (SRs)/meta-analyses (MAs) of acupuncture for low back pain to determine whether acupuncture effectively treats low back pain (LBP). RECENT FINDINGS: Twenty-three SRs/MAs were deemed eligible for the present overview. The AMSTAR 2 score showed that the methodological quality of one SR/MA was of medium quality, one was of low quality, and 21 were of critically low quality. Based on the results of the PRISMA evaluation, there are certain areas for improvement in the quality of reporting of SRs/MAs. There were some reporting flaws in the topic of search strategy (8/23, 34.78%), certainty assessment (4/23, 17.39%), the certainty of evidence (4/23, 17.39%), registration and protocol (3/23, 13.04%), and availability of data, code, and other material (1/23, 4.35%). Results from the GRADE evaluation indicated that 13 of 255 outcomes were rated as moderate, 88 were low, and 154 were very low. Acupuncture effectively treated LBP in the SRs/MAs included in the reevaluation. However, the methodological, report, and evidence-based quality of the SRs/MAs on acupuncture for LBP was low. Therefore, further rigorous and comprehensive studies are warranted to improve the quality of SRs/MAs in this field.

Identification of the anti-inflammatory quality markers of Chrysanthemi Flos (Juhua) using spectrum-effect relationships combined with bioactivity re-evaluation.

Chrysanthemi Flos (Juhua), an edible herbal medicine that possesses efficacies of dispersing wind, clearing heat and detoxifying. Studies have demonstrated that the health benefits of Chrysanthemi Flos are largely attributable to its anti-inflammatory effects. However, the correlation between the compounds monitored by the current quality control methods and the anti-inflammatory effects of Chrysanthemi Flos is unclear. In order to better control the quality of Chrysanthemi Flos, the identification of anti-inflammatory quality markers (Q-markers) of Chrysanthemi Flos was performed. The chemical components of Chrysanthemi Flos were profiled by HPLC fingerprints combined with chemometrics methods. Simultaneously, the anti-inflammatory activities of 10 batches of water extracts of Chrysanthemi Flos were evaluated in lipopolysaccharide-activated RAW 264.7 macrophages cells. Gray correlation analysis was performed to assess the relationship between the anti-inflammatory activity and chemical properties. The results showed that 13 common peaks were closely correlated with the anti-inflammatory effect, and further bioactivity re-evaluation confirmed that 10 known compounds exerted a strong anti-inflammatory effect. The quantitative analysis of the 10 Q-markers showed that the 25 batches of samples could be discriminated into different zones according to their producing areas. Conclusively, the present work identified 10 anti-inflammatory Q-markers of Chrysanthemi Flos using spectrum-effect relationships combined with bioactivity re-evaluation.

[Challenges and Influencial Factors in Autism-Specific Diagnostics in Toddlers]. / Herausforderungen und Einflussfaktoren bei der autismusspezifischen Diagnostik im Kleinkindalter.

Challenges and Influencial Factors in Autism-Specific Diagnostics in Toddlers Abstract. Objective: What are the particular challenges that make early diagnosis of young children difficult in the clinical routine? What recommendations can be derived from this in practice? Methods: Our interdisciplinary social pediatric team examined 31 toddlers aged 2 to 3 years twice in intervals of 6-9 months in the for outpatient diagnostics regarding suspected autism spectrum disorder (ASD). In addition, we conducted an online survey with further experts. Results: After the first anamnestic interview, 8 of the 31 (26 %) children were diagnosed with a differential diagnosis of ASD. Comorbid disorders, familial peculiarities, and challenges posed by the examination setting and anamnesis made a reliable clinical classification difficult. Conclusion: In our experience, many toddlers can only receive a valid diagnosis after a follow-up examination after starting one or more therapies and regularly carrying out these therapies over a period of 6-9 months and possibly also after structural changes have taken place (care in nursery, implementation of youth welfare measures, or similar).

What is the yield of EBUS-TBNA for re-evaluation of previously treated non-small-cell lung cancer?

BACKGROUND: Locoregional recurrence in lung cancer still remains an important problem. We aimed to indicate the effectiveness of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for reevaluation in previously treated nonsmall cell lung cancer (NSCLC). METHODS: : NSCLC patients who underwent EBUS for rebiopsy of suspicious recurrent or progressive lesions between January 2010 and June 2017 were reviewed. Patients were categorized into two groups based on the previous treatment modalities: Group 1 (G1) consisted of patients who had been treated with chemoradiotherapy, and Group 2 (G2) consisted of patients who had undergone radical surgery. RESULTS: Of 115 patients, 100 patients enrolled in the study. Of 26 patients with 35 lymph nodes in G1, malignant cells were identified in thirteen patients (50%). Anthracosis was detected in the remaining. Malignancy was detected in 28 patients (37.8%) in G2. Thirty-threepatients were diagnosed as benign (24 anthracosis; 8 lymphocytes, and 1 granulomatous); 8 were not sampled, and inadequate material was obtained in five. The sensitivity, specificity, negative and positive predictive value, and overall diagnostic accuracy of EBUS-TBNA for rebiopsy in G1 were 84.8%, 100%, 89.1%, 100%, and 93.2%, respectively. These values were all perfect in G2. DISCUSSION: EBUS-TBNA could be preferred as a feasible and efficient procedure for rebiopsy in previously treated NSCLC patients.

[The impact of restaging transurethral resection on recurrence and progression free survival in patients with T1 high grade bladder cancer]. / Résultats et impacts d'une résection de réévaluation dans le traitement des carcinomes urothéliaux de vessie pT1G3 : étude observationnelle.

INTRODUCTION: Restaging transurethral resection (re-TUR) of high grade T1 bladder cancer (HGT1-BC) is recommended but the impact in terms of recurrence-free survival (RFS) and progression-free survival (PFS) is discussed. The objective of this study was to evaluate our practice of re-TUR for these tumors and its impact on overall survival (OS), RFS and PFS. MATERIALS AND METHODS: A retrospective observational study was conducted between 2010 and 2020. The inclusion criteria was the presence of newly diagnosed HGT1-BC. Patients with incomplete resection, suspicion of infiltrating tumor, upper tract urothelial cancer, or metastatic disease were ineligible. Two groups were defined : Group 1 with re-TUR and Group 2 without re-TUR. RFS and PFS were evaluated. RESULTS: A total of 78 patients were included, including 50 (64,1%) in group 1. There were no significant differences between the two groups. The mean time to re-TUR was 8 weeks and 60% residual tumor was found. Initial under-staging was found in 12% of cases. RFS and PFS were significantly better in Group 1 (P=0.0019; P=0,02). No significant were found between the groups in OS and specific survival (SS). CONCLUSION: Performing a re-TUR for high grade T1 bladder tumors allows detection of residual tumor and decreases the risk of under-evaluation. It is associated with a significant improvement in RFS and PFS with no impact on OS and SS.

Re-evaluation of neurobehavioural toxicity of clothianidin using statistical methods for ordered alternatives assuming dose-response effect.

Neurobehavioural toxicity of clothianidin in previous studies was re-evaluated using statistical methods for ordered alternatives assuming a dose-response effect. In a maternal exposure study, clothianidin was added into the diet to provide levels of 0% (control), 0.002%, 0.006% and 0.018% during the gestation and lactation periods in mice. In exploratory behaviour of male offspring in the F1 generation, average speed increased significantly in a dose-related manner in the Jonckheere test. Total distance lengthened in the high-dose group and average speed increased in the high-dose group in the Shirley-Williams test. In a two-generation toxicity study, clothianidin was added in the diet to provide levels of 0% (control), 0.003%, 0.006% and 0.012% from 5 weeks of age of the F0 generation to 11 weeks of age of the F1 generation in mice. The exploratory behaviour of adult males in the F0 generation, the average time of movement, and the number of rearing and rearing time increased significantly in a dose-related manner in the Jonckheere test. The average speed increased in the middle- and high-dose groups, number of rearing increased in the high-dose group and rearing time lengthened in middle- and high-dose groups in the Shirley-Williams test. These results suggest that the use of the appropriate statistical methods adjusted to the objectives of the study and the characteristics of the data could provide more definite conclusions.

[Research progress on adverse reactions and pseudo-allergic reactions of traditional Chinese medicine injections].

Since the safety re-evaluation of traditional Chinese medicine(TCM) injections began in 2009, some TCM injection companies and research institutes have done a lot of work. And with the increase of drug development and drug production technology levels in China, the safety of some TCM injections has been greatly improved. There are safety risks in TCM injections, which are mainly reflected in unclear basis of medicinal materials, simple production process, poor controllability of quality standards, nonstan-dard drug instructions and irrational medication in the use process. This paper describes the research progress of the above-mentioned aspects of TCM injections. In addition, the author team found that adverse reactions of TCM injections are mainly pseudo-allergic reactions. Therefore, a lot of work has been done in detection of pseudo-allergic reactions, mechanism research and risk control. This part of the work is also described in this article.

Postmortem examination protocol and systematic re-evaluation reduce the proportion of unexplained stillbirths.

Background Stillbirth often remains unexplained, mostly due to a lack of any postmortem examination or one that is incomplete and misinterpreted. Methods This retrospective cohort study was conducted at the Department of Obstetrics and Gynecology, Helsinki University Hospital, Finland, and comprised 214 antepartum singleton stillbirths from 2003 to 2015. Maternal and fetal characteristics and the results of the systematic postmortem examination protocol were collected from medical records. Causes of death were divided into 10 specific categories. Re-evaluation of the postmortem examination results followed. Results Based on our systematic protocol, the cause of death was originally defined and reported as such to parents in 133 (62.1%) cases. Re-evaluation of the postmortem examination results revealed the cause of death in an additional 43 (20.1%) cases, with only 23 (10.7%) cases remaining truly unexplained. The most common cause of stillbirth was placental insufficiency in 56 (26.2%) cases. A higher proportion of stillbirths that occurred at ≥39 gestational weeks remained unexplained compared to those that occurred earlier (24.1% vs. 8.6%) (P = 0.02). Conclusion A standardized postmortem examination and a re-evaluation of the results reduced the rate of unexplained stillbirth. Better knowledge of causes of death may have a major impact on the follow-up and outcome of subsequent pregnancies. Also, closer examination and better interpretation of postmortem findings is time-consuming but well worth the effort in order to provide better counseling for the grieving parents.

A Matter of Reevaluation: Incentivizing Users to Contribute Reviews in Online Platforms.

Content sharing platforms such as product review websites largely depend on reviewers' voluntary contributions. In order to motivate reviewers to contribute more, many platforms established incentive mechanisms, either reputation-based or financial. Yet most of the existing research has focused on reputations that are everlasting, such as badges and virtual points, or financial rewards where no evaluation exists about the users' contributed content, such as rebates. There is still a significant gap in our understanding of how incentives with reevaluation mechanism actually influence reviewers' behaviors such as their contribution levels, the opinion they express, and how they express. In this paper, we fill this gap using data collected from Yelp Elite Squad where reviewers with good reviewing history are awarded into the elite group and most importantly reevaluated each year. We draw from the accountability theory and conduct a difference-in-differences analysis to empirically study the effect of incentives with reevaluation mechanism on reviewers' behaviors in both short term and long term. The results show that in short term, reviewers significantly increase their contribution levels, become more conservative with lower percentage of extreme ratings, and also increase the readability of their reviews. In long term, they continue improving the quality of reviews though their numerical rating behaviors stabilize. Our research has significant implications for business models that rely on user contributions.

Reassessment of inappropriate prescriptions of proton pump inhibitors in elderly in-patients: It's time to take action.

OBJECTIVES: To determine the impact of awareness sessions, proposed by the pharmaceutical team to the hospital physicians, on the reassessment of off-label non-hospital proton pump inhibitor prescriptions dedicated to hospitalized patients in the internal medicine department of a university hospital. METHODS: We conducted a retrospective and comparative cohort study of in-patients aged 65 years old and older with a prescription including a proton pump inhibitor. Patients who were admitted before the implementation of the awareness sessions were enrolled in the control group; others were enrolled in the awareness experimental group. The awareness sessions relating to the appropriate use of proton pump inhibitors involved a presentation about the national consensus guidelines, their side effects, the possible drug interactions with this therapeutic class, and recommendations about proton pump inhibitor discontinuation. Discussions took place around clinical cases during this multidisciplinary meeting. RESULTS: In total, 105 patients were included in the control group, and 52 in the awareness experimental group. In total, 10.8% of the non-hospital prescriptions were in accordance with the guidelines. The spontaneous reassessment of non-hospital proton pump inhibitors prescriptions was significantly higher in the experimental group (55.6%) compared to the control group (35.8%) (P=0.02). At discharge, 66.7% of the off-label non-hospital proton pump inhibitor prescriptions were reassessed in the experimental group versus 28.4% in the control group P<0.01). CONCLUSIONS: This multidisciplinary team meetings on the appropriate use of proton pump inhibitors were proved effective to improve prescription conformity to guidelines in older patients.

The concept of leukaemic stem cells in acute myeloid leukaemia 25 years on: hitting a moving target.

The concept of leukaemic stem cells (LSCs) was experimentally suggested 25 years ago through seminal data from John Dick's group, who showed that a small fraction of cells from acute myeloid leukaemia (AML) patients were able to be adoptively transferred into immunodeficient mice. The initial estimation of the frequency was 1:250 000 leukaemic cells, clearly indicating the difficulties ahead in translating knowledge on LSCs to the clinical setting. However, the field has steadily grown in interest, expanse and importance, concomitantly with the realisation of the molecular background for AML culminating in the sequencing of hundreds of AML genomes. The literature is now ripe with contributions describing how different molecular aberrations are more or less specific for LSCs, as well as reports showing selectivity in targeting LSCs in comparison to normal haematopoietic stem and progenitor cells. However, we argue here that these important data have not yet been fully realised within the clinical setting. In this clinically focused review, we outline the difficulties in identifying and defining LSCs at the individual patient level, with special emphasis on intraclonal heterogeneity. In addition, we suggest areas of future focus in order to realise the concept as real-time benefit for AML patients.

Improved diagnostics by exome sequencing following raw data reevaluation by clinical geneticists involved in the medical care of the individuals tested.

PURPOSE: Reanalysis of exome sequencing data when results are negative may yield additional diagnoses. We sought to estimate the contribution of clinical geneticists to the interpretation of sequencing data of their patients. METHODS: The cohort included 84 probands attending a tertiary genetics institute (2015-2018) with a nondiagnostic result on clinical exome sequencing performed in one of five external laboratories. The raw data were uploaded to the Emedgene bioinformatics and interpretation platform for reanalysis by a team of two clinical geneticists, the geneticist directly involved in the patient's care, and a bioinformatician. RESULTS: In ten probands (11.9%), a new definitive diagnosis was reached based on genes that were known to be associated with the phenotype at the time the original report was issued. The main reasons for a negative exome result were incorrect interpretation of the clinical context and absence of OMIM entry. Pathogenic variants in genes with previously unknown gene-disease associations were discovered to be causative in three probands. In total, new diagnoses were established in 13/84 individuals (15.5%). CONCLUSION: Direct access to complete clinical data and shortening of time to including gene-phenotype associations in databases can assist the analytics team and reduce the need for additional unnecessary tests.

The progression of the ClinGen gene clinical validity classification over time.

In order for ClinGen to maintain up-to-date gene-disease clinical validity classifications for use by clinicians and clinical laboratories, an appropriate timeline for reevaluating curated gene-disease associations will need to be determined. To provide guidance on how often a gene-disease association should be recurated, a retrospective analysis of 30 gene curations was performed. Curations were simulated at one-year intervals starting with the year of the first publication to assert disease-causing variants in the gene to observe trends in the classification over time, as well as factors that influenced changes in classification. On average, gene-disease associations spent the least amount of time in the "Moderate" classification before progressing to "Strong" or "Definitive." In contrast, gene-disease associations that spent five or more years in the "Limited" classification were most likely to remain "Limited" or become "Disputed/Refuted." Large population datasets contributed to the reclassification of several gene-disease associations from "Limited" to "Disputed/Refuted." Finally, recent advancements in sequencing technology correlated with an increase in the quantity of case-level evidence that was curated per paper. This study provided a number of key points to consider when determining how often to recurate a gene-disease association.

Marked yield of re-evaluating phenotype and exome/target sequencing data in 33 individuals with intellectual disabilities.

The diagnosis of intellectual disability/developmental delay (ID/DD) benefits from the clinical application of target/exome sequencing. The yield in Mendelian diseases varies from 25% to 68%. The aim of the present study was to identify the genetic causes of 33 ID/DD patients using target/exome sequencing. Recent studies have demonstrated that reanalyzing undiagnosed exomes could yield additional diagnosis. Therefore, in addition to the normal data analysis, in this study, re-evaluation was performed prior to manuscript preparation after updating OMIM annotations, calling copy number variations (CNVs) and reviewing the current literature. Molecular diagnosis was obtained for 19/33 patients in the first round of analysis. Notably, five patients were diagnosed during the re-evaluation of the geno/phenotypic data. This study confirmed the utility of exome sequencing in the diagnosis of ID/DD. Furthermore, re-evaluation leads to a 15% improvement in diagnostic yield. Thus, to maximize the diagnostic yield of next-generation sequencing (NGS), periodical re-evaluation of the geno/phenotypic data of undiagnosed individuals is recommended by updating the OMIM annotation, applying new algorithms, reviewing the literature, sharing pheno/genotypic data, and re-contacting patients.

Caffeine alters emotion and emotional responses in low habitual caffeine consumers.

Caffeine reliably increases emotional arousal, but it is unclear whether and how it influences other dimensions of emotion such as emotional valence. These experiments documented whether caffeine influences emotion and emotion regulation choice and success. Low to abstinent caffeine consumers (maximum 100 mg/day) completed measures of state anxiety, positive and negative emotion, and salivary cortisol before, 45 min after, and 75 min after consuming 400 mg caffeine or placebo. Participants also completed an emotion regulation choice task, in which they chose to employ cognitive reappraisal or distraction in response to high and low intensity negative pictures (Experiment 1), or a cognitive reappraisal task, in which they employed cognitive reappraisal or no emotion regulation strategy in response to negative and neutral pictures (Experiment 2). State anxiety, negative emotion, and salivary cortisol were heightened both 45 and 75 min after caffeine intake relative to placebo. In Experiment 1, caffeine did not influence the frequency with which participants chose reappraisal or distraction, but reduced negativity of the picture ratings. In Experiment 2, caffeine did not influence cognitive reappraisal success. Thus, caffeine mitigated emotional responses to negative situations, but not how participants chose to regulate such responses or the success with which they did so.

Influence of operator skill level on the clinical outcome of non-surgical periodontal treatment: a retrospective study.

OBJECTIVES: The aim of this study is to evaluate the effect of operators experience and skill on treatment results of initial non-surgical periodontal therapy. MATERIALS AND METHODS: Initial periodontal treatment was carried out by either second-year periodontal residents (PR) or last year dental students (DS). From the treatment records of patients in each group, plaque and bleeding indices, and pocket depth (PD) at baseline and at re-evaluation were collected retrospectively on each tooth at six locations. Data were separated according to tooth type, area, and probing depth categories, sub-grouped to 1-3, 4-5, and ≥ 6 mm. RESULTS: Fifty and 49 records of DS and PR patients, accordingly, were analyzed. Initial periodontal treatment improved patient compliance in both groups and reduced signs of inflammation with significantly superior results in the PR group. Significant change in percentage of pockets was recorded in each category. The increase in percentage of sites with PD 1-3 mm and decrease in percentage of PD ≥ 6 mm pockets was significantly (p ≤ 0.001) superior in patients treated by PR. Percentage of 4-5 mm pockets was significantly reduced in both groups (p ≤ 0.01), with a significantly greater reduction in the mandibular molar and anterior teeth in the PR group. CONCLUSIONS: Experience and skill significantly affect the outcome of non-surgical periodontal therapy, with more positive improvement in patient compliance and clinical parameters when performed by a more qualified operator. CLINICAL RELEVANCE: Improvement of operator skills may decrease the number of residual pockets and increase patient compliance following non-surgical periodontal treatment.

Analyzing Evolutionary Optimization in Noisy Environments.

Many optimization tasks must be handled in noisy environments, where the exact evaluation of a solution cannot be obtained, only a noisy one. For optimization of noisy tasks, evolutionary algorithms (EAs), a type of stochastic metaheuristic search algorithm, have been widely and successfully applied. Previous work mainly focuses on the empirical study and design of EAs for optimization under noisy conditions, while the theoretical understandings are largely insufficient. In this study, we first investigate how noisy fitness can affect the running time of EAs. Two kinds of noise-helpful problems are identified, on which the EAs will run faster with the presence of noise, and thus the noise should not be handled. Second, on a representative noise-harmful problem in which the noise has a strong negative effect, we examine two commonly employed mechanisms dealing with noise in EAs: reevaluation and threshold selection. The analysis discloses that using these two strategies simultaneously is effective for the one-bit noise but ineffective for the asymmetric one-bit noise. Smooth threshold selection is then proposed, which can be proved to be an effective strategy to further improve the noise tolerance ability in the problem. We then complement the theoretical analysis by experiments on both synthetic problems as well as two combinatorial problems, the minimum spanning tree and the maximum matching. The experimental results agree with the theoretical findings and also show that the proposed smooth threshold selection can deal with the noise better.