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Human Reproduction (Oxford, England) Jun 2024Are markers of epigenetic age acceleration in follicular fluid associated with outcomes of ovarian stimulation?
STUDY QUESTION
Are markers of epigenetic age acceleration in follicular fluid associated with outcomes of ovarian stimulation?
SUMMARY ANSWER
Increased epigenetic age acceleration of follicular fluid using the Horvath clock, but not other epigenetic clocks (GrimAge and Granulosa Cell), was associated with lower peak estradiol levels and decreased number of total and mature oocytes.
WHAT IS KNOWN ALREADY
In granulosa cells, there are inconsistent findings between epigenetic age acceleration and ovarian response outcomes.
STUDY DESIGN, SIZE, DURATION
Our study included 61 women undergoing IVF at an academic fertility clinic in the New England area who were part of the Environment and Reproductive Health Study (2006-2016).
PARTICIPANTS/MATERIALS, SETTING, METHODS
Participants provided a follicular fluid sample during oocyte retrieval. DNA methylation of follicular fluid was assessed using a genome-wide methylation screening tool. Three established epigenetic clocks (Horvath, GrimAge, and Granulosa Cell) were used to predict DNA-methylation-based epigenetic age. To calculate the age acceleration, we regressed epigenetic age on chronological age and extracted the residuals. The association between epigenetic age acceleration and ovarian response outcomes (peak estradiol levels, follicle stimulation hormone, number of total, and mature oocytes) was assessed using linear and Poisson regression adjusted for chronological age, three surrogate variables (to account for cellular heterogeneity), race, smoking status, initial infertility diagnosis, and stimulation protocol.
MAIN RESULTS AND ROLE OF CHANCE
Compared to the median chronological age of our participants (34 years), the Horvath clock predicted, on an average, a younger epigenetic age (median: 24.2 years) while the GrimAge (median: 38.6 years) and Granulosa Cell (median: 39.0 years) clocks predicted, on an average, an older epigenetic age. Age acceleration based on the Horvath clock was associated with lower peak estradiol levels (-819.4 unit decrease in peak estradiol levels per standard deviation increase; 95% CI: -1265.7, -373.1) and fewer total (% change in total oocytes retrieved per standard deviation increase: -21.8%; 95% CI: -37.1%, -2.8%) and mature oocytes retrieved (% change in mature oocytes retrieved per standard deviation increase: -23.8%; 95% CI: -39.9%, -3.4%). The age acceleration based on the two other epigenetic clocks was not associated with markers of ovarian response.
LIMITATIONS, REASONS FOR CAUTION
Our sample size was small and we did not specifically isolate granulosa cells from follicular fluid samples so our samples could have included mixed cell types.
WIDER IMPLICATIONS OF THE FINDINGS
Our results highlight that certain epigenetic clocks may be predictive of ovarian stimulation outcomes when applied to follicular fluid; however, the inconsistent findings for specific clocks across studies indicate a need for further research to better understand the clinical utility of epigenetic clocks to improve IVF treatment.
STUDY FUNDING/COMPETING INTEREST(S)
The study was supported by grants ES009718, ES022955, ES000002, and ES026648 from the National Institute of Environmental Health Sciences (NIEHS) and a pilot grant from the NIEHS-funded HERCULES Center at Emory University (P30 ES019776). RBH was supported by the Emory University NIH Training Grant (T32-ES012870).
TRIAL REGISTRATION NUMBER
N/A.
PubMed: 38890131
DOI: 10.1093/humrep/deae136 -
Journal of Applied Clinical Medical... Jun 2024Novel on-board CBCT allows for improved image quality and Hounsfield unit accuracy. When coupled with online adaptive tools, this may have potential to allow for...
BACKGROUND
Novel on-board CBCT allows for improved image quality and Hounsfield unit accuracy. When coupled with online adaptive tools, this may have potential to allow for simulation and treatment to be completed in a single on-table session.
PURPOSE
To study the feasibility of a high-efficiency radiotherapy treatment workflow without the use of a separate session for simulation imaging. The dosimetric accuracy, overall efficiency, and technical feasibility were used to evaluate the clinical potential of CT simulation-free adaptive radiotherapy.
METHODS
Varian's Ethos adaptive radiotherapy treatment platform was upgraded with a novel CBCT system, HyperSight which reports image quality and Hounsfield unit accuracy specifications comparable to standard fan-beam CT. Using in-house developed MATLAB software, CBCT images were imported into the system and used for planning. Two test cases were completed on anthropomorphic phantoms equipped with small volume ion chambers (cross-calibrated to an ADCL traceable dose standard) to evaluate the feasibility and accuracy of the workflows. A simulated palliative spine treatment was planned with 8 Gy in one fraction, and an intact prostate treatment was planned with 60 Gy in 20 fractions. The CBCTs were acquired using HyperSight with default thorax and pelvis imaging protocols and reconstructed using an iterative algorithm with scatter removal, iCBCT Acuros. CBCTs were used for contouring and planning, and treatment was delivered via an online adaptive workflow. In addition, an external dosimetry audit was completed using only on-board CBCT imaging in an end-to-end head and neck phantom irradiation.
RESULTS
An extended-field CBCT acquisition can be acquired in 12 s, in addition to the time for longitudinal table shifts, and reconstructed in approximately 1 min. The superior-inferior extent for the CBCT planning images was 38.2 cm, which captured the full extent of relevant anatomy. The contouring and treatment planning for the spine and prostate were completed in 30 and 18 min, respectively. The dosimetric agreement between ion chamber measurements and the treatment plan was within a range of -1.4 to 1.6%, and a mean and standard deviation of 0.41 ± 1.16%. All metrics used in the external audit met the passing criteria, and the dosimetric comparison between fan-beam and CBCT techniques had a gamma passing rate of 99.0% with a criteria of 2%/2 mm.
CONCLUSION
Using an in-house workflow, CT simulation-free radiation therapy was shown to be feasible with acceptable workflow efficiency and dosimetric accuracy. This approach may be particularly applicable for urgent palliative treatments. With the availability of software to enable this workflow, and the continued advancement of on-treatment adaptation, single-visit radiation therapy may replace current practice for some clinical indications.
PubMed: 38889325
DOI: 10.1002/acm2.14438 -
Clinical and Translational... Jun 2024The diagnosis of eosinophilic gastrointestinal diseases is largely based on mucosal eosinophil counts, but thresholds and normal ranges beyond the esophagus are debated,...
OBJECTIVES
The diagnosis of eosinophilic gastrointestinal diseases is largely based on mucosal eosinophil counts, but thresholds and normal ranges beyond the esophagus are debated, calling for much-needed methodological standardization. We aimed to develop a standardized workflow for duodenal cell quantification and estimate duodenal eosinophil and mast cell numbers in healthy controls.
METHODS
Software-based histological cell quantification using free-sized or fixed-sized regions was developed and applied to digitized hematoxylin and eosin (H&E) stained slides from 58 individuals (healthy controls (HC) and functional dyspepsia (FD) patients). Intraclass correlation coefficients (ICC) compared interrater reliability between software-based and microscopic quantification. Reproducibility of the software-based method was validated in an independent cohort of 37 control and FD subjects. Eosinophil identification on H&E staining was compared to immunohistochemistry (IHC). Normal eosinophil (H&E) and mast cell (cKit) ranges were determined in 70 adult HC.
RESULTS
Eosinophil quantification on digitized slides demonstrated excellent (ICC: 0.909) and significantly improved reproducibility over microscopic evaluation (ICC: 0.796, P = .0014), validated in an independent cohort (ICC: 0.910). Duodenal eosinophils were more abundant around crypts than in villi (P < .0001), while counts were similar on matched H&E and IHC stained slides (P = .55). Mean ± standard deviation (95th percentile) duodenal eosinophils and mast cells in HC were 228.8/mm2 ± 94.7 (402.8/mm2) and 419.5/mm2 ± 132.2 (707.6/mm2), respectively.
CONCLUSION
We developed and validated a standardized approach to duodenal histological cell quantification, generalizable to various mucosal cell types. Implementation of software-based quantification identified 400 eosinophils/mm2 and 700 mast cells/mm2 as thresholds for abnormal duodenal infiltration.
PubMed: 38888240
DOI: 10.14309/ctg.0000000000000725 -
Analytical Methods : Advancing Methods... Jul 2024Organophosphate esters (OPEs) are widely used as flame retardants and plasticizers, which are of growing concern due to their endocrine-disrupting effects, developmental...
Organophosphate esters (OPEs) are widely used as flame retardants and plasticizers, which are of growing concern due to their endocrine-disrupting effects, developmental toxicity, and potential carcinogenicity. However, data on human exposure to OPEs is still scarce. In this study, a relatively simple and efficient method with less serum consumption for the detection of OPEs in human serum was developed and validated. Nine OPEs in 200 μL of human serum were extracted by an acetonitrile-formic acid system and analyzed using ultra-high-performance liquid chromatography-quadrupole tandem time-of-flight high-resolution mass spectrometry. Several experiments were conducted to optimize the chromatographic and mass spectrometric conditions as well as sample preparation to obtain a more sensitive and efficient analytical protocol. The proposed method was examined in terms of its linearity, accuracy, precision, detection limit, and matrix effect. The matrix-spiked recoveries of the target OPEs ranged from 83.3% to 111.1%, with relative standard deviations between 2.7% and 16.6%. The detection limits were within (0.002 to 0.029) ng mL, while the quantification limits were within (0.007 to 0.098) ng mL. The internal standard-corrected matrix effects varied from 82.7% to 113.9%. Finally, the method was applied to detect OPEs in actual human serum samples. All nine OPEs were detected in 269 serum samples to varying degrees, with the average concentrations ranging from (0.08 to 1.77) ng mL. After validation, the method was found to be simple in pretreatment, high in sensitivity, good in practicality, and suitable for exposure evaluation of OPEs in populations.
Topics: Humans; Esters; Organophosphates; Chromatography, High Pressure Liquid; Limit of Detection; Tandem Mass Spectrometry; Reproducibility of Results; Chromatography, Liquid; Flame Retardants; Mass Spectrometry; Liquid Chromatography-Mass Spectrometry
PubMed: 38887095
DOI: 10.1039/d4ay00787e -
Veterinary Medicine and Science Jul 2024The public perception relating to the welfare of horses involved with equestrian sports is associated with training methods used and the presentation of horses at...
BACKGROUND/OBJECTIVES
The public perception relating to the welfare of horses involved with equestrian sports is associated with training methods used and the presentation of horses at events. In this context, very tight nosebands, which are intended to prevent the horse from opening its mouth, also attract a lot of attention. Various studies have evaluated the impact of tight nosebands on stress parameters, whereas the effect of tight nosebands on upper airway function is unknown. Therefore, the aim of the study was to use overground endoscopy to evaluate changes in pharyngeal and laryngeal function when a tight noseband is fitted. Moreover, the ridden horse pain ethogram (RHpE) was applied to investigate signs of discomfort (Dyson et al., 2018).
STUDY DESIGN
A randomized, blinded, and prospective study was performed.
METHODS
Sixteen warmblood horses consisting of twelve mares and four geldings with a mean age of 11.63 ± 3.53 years were ridden on 2 consecutive days with either loose or tight nosebands (two fingers or no space between bridge of the nose and noseband, respectively) and inserted endoscope in a random order. Videos were taken in a riding arena during a standardized exercise protocol involving beginner level tasks for 30 min in all gaits. For video analysis, freeze frames were prepared and analyzed at the beginning of the expiration phase. Pharyngeal diameter was measured using the pharynx-epiglottis ratio. Other findings (swallowing, pharyngeal collapse, soft palate movements, and secretion) were also evaluated. Moreover, the RHpE was applied. Descriptive statistics and generalized linear mixed effects models were used. Results with a p-value < 0.05 were considered statistically significant.
RESULTS
While the pharynx-epiglottis ratio did not change significantly in horses ridden with loose versus tight nosebands, there was an increase in mean grade and total counts of parameters assessed in the pharyngeal region, for example, grade of secretion (1.5 [±SD 0.89] vs. 3.13 [±SD 0.96]; p = 0.0001), axial deviation of the aryepiglottic folds (0.29 [±SD 0.73] vs. 1.33 [±SD 1.44]; p = 0.01), and pharyngeal collapse (0.69 [±SD 0.87] vs. 1.88 [±SD 1.54]; p = 0.005) in horses ridden with tight nosebands. There was no RHpE score above 8 indicating musculoskeletal pain, but the RHpE scores were significantly higher in horses ridden with tight nosebands (p < 0.001).
MAIN LIMITATIONS
Video quality was limited when horses showed large amounts of secretion. Another limitation was the small number of horses.
CONCLUSIONS
Results add to the evidence obtained in other studies that tight nosebands do not only cause adverse reactions based on the RHpE score such as head behind the vertical or intense staring but also contribute to changes in the pharyngeal region, such as increased secretion and collapse of pharyngeal structures. This may provide further support for future decisions regarding regulations on nosebands.
Topics: Animals; Horses; Female; Male; Prospective Studies; Pharynx; Nose; Larynx; Physical Conditioning, Animal
PubMed: 38885311
DOI: 10.1002/vms3.1478 -
Journal of Medical Systems Jun 2024The rapid development of the digital healthcare and the electronic health records (EHR) requires smooth networking infrastructure to access data using Hypertext Transfer...
The rapid development of the digital healthcare and the electronic health records (EHR) requires smooth networking infrastructure to access data using Hypertext Transfer Protocol (HTTP)-based applications. The new HTTP/3 standard should provide performance and security improvements over HTTP/2. The goal of our work was to test the performance of HTTP/2 and HTTP/3 in the context of the EHRs. We used 45,000 test FHIR Patient resources downloaded and uploaded using 20, 50, 100 and 200 resources per Bundle, which resulted in 2251, 901, 451 and 226 HTTP GET and POST requests respectively. The first test downloading 20 resources per Bundle showed that HTTP/3 outperformed HTTP/2 in the local (mean request time 16.57 ms ± 7.2 standard deviation [SD]) and in the remote network (71.45 ms ± 43.5 SD) which is almost 3 times faster. In the 50 and 100 resources per Bundle test the HTTP/3 protocol demonstrated again more than two times gain in downloading performance for remote requests with mean request time 91.13 ms ± 34.54 SD and 88.09 ms ± 21.66 SD respectively. Furthermore, HTTP/3 outperformed HTTP/2 in the constructed clinical dataset remote transfer. In the upload tests HTTP/3 showed only a slight gain in performance merely in the remote network. The HTTP/3 protocol is a relatively new development and a major improvement for the worldwide web. This new technology is still missing in the digital health and EHRs. Its use could offer a major performance gain in situations where data is gathered from multiple remote locations.
Topics: Electronic Health Records; Humans; Computer Security; Computer Communication Networks; Internet
PubMed: 38878183
DOI: 10.1007/s10916-024-02080-0 -
Applied Spectroscopy Jun 2024The use of Raman spectroscopy has rapidly been on the rise across a great number of industries where comparability, reproducibility, and reliability of the data are of...
The use of Raman spectroscopy has rapidly been on the rise across a great number of industries where comparability, reproducibility, and reliability of the data are of paramount importance. However, controlling the intensity of the Raman signal depends on a large number of factors such as the wavelength of the laser light, the optical components of each device, or the number of molecules in the illuminated volume. For this reason, in this study, a new protocol has been applied to twin Raman devices to achieve a conversion of the signal between them, by pairing the intensity response of the units using a reference sample. The new reference material is a homogenous dispersion of a 0.5 wt% anatase (titanium dioxide, or TiO) in an epoxy resin matrix, with deviations <2.5% in Raman intensity across the reference material. The proposed protocol for Raman-twinned devices takes a well-defined approach that leads to obtaining a correction factor that relates the differences in the signal intensity between the two Raman devices, in order to obtain the same Raman intensity counts. The performance of the proposed method was evaluated based on the data from the devices, which presented the most common user cases: twinning Raman devices of the non-confocal same model for two different wavelengths; and twinning confocal and non-confocal devices. The results obtained show that the protocol has worked for both of the Raman twinning cases, allowing the Raman intensity harmonization of Raman spectra between two different devices.
PubMed: 38876969
DOI: 10.1177/00037028241260377 -
PLoS Medicine Jun 2024Few cost-effective strategies to shift dietary habits of populations in a healthier direction have been identified. We examined if participating in a chatbot health... (Randomized Controlled Trial)
Randomized Controlled Trial
An SMS chatbot digital educational program to increase healthy eating behaviors in adolescence: A multifactorial randomized controlled trial among 7,890 participants in the Danish National Birth Cohort.
BACKGROUND
Few cost-effective strategies to shift dietary habits of populations in a healthier direction have been identified. We examined if participating in a chatbot health education program transmitted by Short Messages Service ("SMS-program") could improve adolescent dietary behaviors and body weight trajectories. We also explored possible added effects of maternal or peer involvement.
METHODS AND FINDINGS
We conducted a randomized controlled trial (RCT) among adolescents from the Danish National Birth Cohort (DNBC). Eligible were adolescents who during 2015 to 2016 at age 14 years had completed a questionnaire assessing height, weight, and dietary habits. Two thirds were offered participation in an SMS-program, whereas 1/3 ("non-SMS group") received no offer. The SMS program aimed to improve 3 key dietary intake behaviors: sugar-sweetened beverages (SSBs), fruit and vegetables (FV), and fish. The offered programs had 3 factorially randomized schemes; the aims of these were to test effect of asking the mother or a friend to also participate in the health promotion program, and to test the effect of a 4-week individually tailored SMS program against the full 12-week SMS program targeting all 3 dietary factors. Height and weight and intakes of SSB, FV, and fish were assessed twice by a smartphone-based abbreviated dietary questionnaire completed at 6 months (m) and 18 m follow-up. Main outcome measures were (1) body mass index (BMI) z-score; and (2) an abbreviated Healthy Eating Index (mini-HEI, 1 m window, as mean of z-scores for SSB, FV, and fish). Among the 7,890 randomized adolescents, 5,260 were assigned to any SMS program; 63% (3,338) joined the offered program. Among the 7,890 randomized, 74% (5,853) and 68% (5,370) responded to follow-ups at 6 m and 18 m, respectively. Effects were estimated by intention-to-treat (ITT) analyses and inverse probability weighted per-protocol (IPW-PP) analyses excluding adolescents who did not join the program. Mean (standard deviation (SD)) mini-HEI at baseline, 6 m and 18 m was -0.01 (0.64), 0.01 (0.59), and -0.01 (0.59), respectively. In ITT-analyses, no effects were observed, at any time point, in those who had received any SMS program compared to the non-SMS group, on BMI z-score (6 m: -0.010 [95% confidence interval (CI) -0.035, 0.015]; p = 0.442, 18 m: 0.002 [95% CI -0.029, 0.033]; p = 0.901) or mini-HEI (6 m: 0.016 [95% CI -0.011, 0.043]; p = 0.253, 18m: -0.016 [95% CI -0.045, 0.013]; p = 0.286). In IPW-PP analyses, at 6 m, a small decrease in BMI z-score (-0.030 [95% CI -0.057, -0.003]; p = 0.032) was observed, whereas no significant effect was observed in mini-HEI (0.027 [95% CI -0.002, 0.056]; p = 0.072), among those who had received any SMS program compared to the non-SMS group. At 18 m, no associations were observed (BMI z-score: -0.006 [95% CI -0.039, 0.027]; p = 0.724, and mini-HEI: -0.005 [95% CI -0.036, 0.026]; p = 0.755). The main limitations of the study were that DNBC participants, though derived from the general population, tend to have higher socioeconomic status than average, and that outcome measures were self-reported.
CONCLUSIONS
In this study, a chatbot health education program delivered through an SMS program had no effect on dietary habits or weight trajectories in ITT analyses. However, IPW-PP-analyses, based on those 63% who had joined the offered SMS program, suggested modest improvements in weight development at 6 m, which had faded at 18 m. Future research should focus on developing gender-specific messaging programs including "booster" messages to obtain sustained engagement.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02809196 https://clinicaltrials.gov/study/NCT02809196.
Topics: Humans; Female; Adolescent; Denmark; Male; Diet, Healthy; Text Messaging; Feeding Behavior; Health Promotion; Health Education; Adolescent Behavior; Health Behavior; Cohort Studies; Surveys and Questionnaires
PubMed: 38875292
DOI: 10.1371/journal.pmed.1004383 -
Trials Jun 2024The TRANSLATE (TRANSrectal biopsy versus Local Anaesthetic Transperineal biopsy Evaluation) trial assesses the clinical and cost-effectiveness of two biopsy procedures...
Statistical analysis plan for the TRANSLATE (TRANSrectal biopsy versus Local Anaesthetic Transperineal biopsy Evaluation of potentially clinically significant prostate cancer) multicentre randomised controlled trial.
BACKGROUND
The TRANSLATE (TRANSrectal biopsy versus Local Anaesthetic Transperineal biopsy Evaluation) trial assesses the clinical and cost-effectiveness of two biopsy procedures in terms of detection of clinically significant prostate cancer (PCa). This article describes the statistical analysis plan (SAP) for the TRANSLATE randomised controlled trial (RCT).
METHODS/DESIGN
TRANSLATE is a parallel, superiority, multicentre RCT. Biopsy-naïve men aged ≥ 18 years requiring a prostate biopsy for suspicion of possible PCa are randomised (computer-generated 1:1 allocation ratio) to one of two biopsy procedures: transrectal (TRUS) or local anaesthetic transperineal (LATP) biopsy. The primary outcome is the difference in detection rates of clinically significant PCa (defined as Gleason Grade Group ≥ 2, i.e. any Gleason pattern ≥ 4 disease) between the two biopsy procedures. Secondary outcome measures are th eProBE questionnaire (Perception Part and General Symptoms) and International Index of Erectile Function (IIEF, Domain A) scores, International Prostate Symptom Score (IPSS) values, EQ-5D-5L scores, resource use, infection rates, complications, and serious adverse events. We describe in detail the sample size calculation, statistical models used for the analysis, handling of missing data, and planned sensitivity and subgroup analyses. This SAP was pre-specified, written and submitted without prior knowledge of the trial results.
DISCUSSION
Publication of the TRANSLATE trial SAP aims to increase the transparency of the data analysis and reduce the risk of outcome reporting bias. Any deviations from the current SAP will be described and justified in the final study report and results publication.
TRIAL REGISTRATION
International Standard Randomised Controlled Trial Number ISRCTN98159689, registered on 28 January 2021 and registered on the ClinicalTrials.gov (NCT05179694) trials registry.
Topics: Humans; Male; Prostatic Neoplasms; Biopsy; Multicenter Studies as Topic; Anesthesia, Local; Data Interpretation, Statistical; Cost-Benefit Analysis; Neoplasm Grading; Perineum; Randomized Controlled Trials as Topic; Equivalence Trials as Topic; Prostate; Rectum; Predictive Value of Tests
PubMed: 38872174
DOI: 10.1186/s13063-024-08224-4 -
BMC Oral Health Jun 2024Recently, trials have supported changes in deep caries management. However, reporting might lack details, affecting interpretation and implementation. Thus, we aimed to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Recently, trials have supported changes in deep caries management. However, reporting might lack details, affecting interpretation and implementation. Thus, we aimed to evaluate the adherence to the CONSORT statement and the risk of bias of randomized controlled trials (RCTs) on deep caries management published in pediatric dental journals.
METHODS
We searched PubMed for RCTs in six pediatric dental journals between 2010 and 2022, focusing on deep caries lesion management. Adherence to the CONSORT guideline and the risk of bias were assessed using a modified tool with 19 items; each scored from 0 to 2 (maximum of 38 points), and the Cochrane risk-of-bias (RoB 2) tool. We performed descriptive and regression analyses (α = 5%).
RESULTS
We analyzed 127 RCTs. The mean (standard deviation) CONSORT adherence score was 21.1 (6.7). Notably, 96.1% of the studies received a score of 2 for the "intervention" item, whereas 83.5% scored 0 for the "estimated effect size". The risk of bias assessment revealed that 40.2% of the RCTs were at high risk, 59% were at low risk, and 0.8% were at low risk. RCTs with a high risk of bias had lower CONSORT scores (p<0.001) than those with low or some concerns. RCTs published in journals without the endorsement of the CONSORT statement had lower scores than those in journals with the endorsement of the CONSORT statement. Older RCTs (6-10 years old and more than 10 years old) showed significantly lower CONSORT statement compliance than trials published recently within 5 years.
CONCLUSION
Adherence to the CONSORT was relatively low among the investigated RCTs. Moreover, lower adherence to the CONSORT was associated with a higher risk of bias.
TRIAL REGISTRATION
This study protocol was prospectively registered on the Open Science Framework - DOI ( 10.17605/OSF.IO/V6SYZ ).
Topics: Dental Caries; Humans; Randomized Controlled Trials as Topic; Bias; Guideline Adherence
PubMed: 38872165
DOI: 10.1186/s12903-024-04417-0