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Study design and participants
This cross-sectional analysis is based on the baseline data of the “Safer Cycling in Older Age” (SiFAr) project, a parallel group, randomized controlled intervention study with a duration of 3 years aiming to improve cycle competence by a structured training program on the bicycle (June 2020- August 2022). The results ...
PMC10261245
Ethics and study registration
The study protocol was approved by the ethics committee of the Friedrich-Alexander-Universität Erlangen-Nürnberg and was performed in accordance with the guidelines published in the Declaration of Helsinki. The study was registered at ClinicalTrials.gov (identifier: NCT04362514). Written informed consent was obtained f...
PMC10261245
Data collection and measures
Baseline data collection took place between April and June in person in the study center (participants’ characteristics, functional and psychological assessments) and in the outdoor cycle course (performance in the cycle course). All test appointments were scheduled as morning sessions. Demographics, health characteris...
PMC10261245
Health and functional assessments
Functional status was evaluated with the Short Physical Performance Battery (SPPB) testing three different domains of physical function: balance (side-by-side, semi-tandem, tandem stand), usual gait speed (4 m), and strength in lower extremities (5-repetition sit-to-stand). As suggested by Guralnik et al. [
PMC10261245
Cycling skills assessment
Cycling performance was tested in a standardized cycle course with 7 tasks in the order specified (slalom, slow cycling, dismounting into a hula hoop and getting on the bicycle on both sides, cycling through a narrow alley, turning to the off-side, precise braking). Detailed description of the cycling course can be fou...
PMC10261245
Statistical analysis
Statistical analysis was performed using SPSS Version 28 (IBM SPSS Statistics, Chigaco, IL, USA).Participants’ characteristics are presented as median and interquartile range (IQR) for continuous variables as they were not normally distributed. Dichotomous and categorical variables are shown as absolute numbers and per...
PMC10261245
Results
PMC10261245
Limitations in cycling skills
With the exception of As a sub analyses, we investigated via Chi-square tests whether the use of compensatory cycling strategies differed between women and men (see Fig. Use of compensatory cycling skills in women and men Descriptively, women seem to use all compensatory strategies more often men. However, if tested, s...
PMC10261245
Acknowledgements
This paper is submitted in partial fulfilment of the requirements for obtaining the degree Dr. rer. biol. hum. (PhD in human biology) for the primary author.
PMC10261245
Author contributions
V.K., H.M.S, S.K., R.K., C.C.S. and E.F. conceived and designed the trial. V.K., H.M.S. and S.K. conceptualized the manuscript. V.K. and S.K. wrote the paper and H.M.S, R.K., C.C.S., E.F. revised it critically. All authors have read and approved the final version of the manuscript.
PMC10261245
Funding
Open Access funding enabled and organized by Projekt DEAL. This work was funded by a German non-profit foundation (ADAC Stiftung). The funding organization provides the budget for the project and controls that the received money is solely used for the study. Besides this, it has no further role and does not act as a sp...
PMC10261245
Data Availability
The datasets used and/or analysed during the study are available from the corresponding author on reasonable request.
PMC10261245
Declarations
PMC10261245
Conflict of interest
All other authors declare no conflict of interest.
PMC10261245
Ethical approval
The study was performed in accordance with the ethical standards of the ethical committee of the local university and with the 1964 Helsinki declaration and its later amendments. This article does not contain any studies with animals performed by any of the authors. This study was approved by the Friedrich-Alexander-Un...
PMC10261245
Informed consent
All participants provided informed consent prior to their participation.
PMC10261245
References
PMC10261245
1. Introduction
cancer, deaths, breast cancer
CANCER, BREAST CANCER
Soy intake is associated with lower breast cancer risk in observational studies concerning Asian women, however, no randomized controlled trials (RCT) have been conducted among Asian women living in Asia. This three-armed RCT assessed the effects of one-year soy isoflavone (ISF) intervention on mammographic density (MD...
PMC9862880
2. Materials and Methods
PMC9862880
2.1. Study Participants
RECRUITMENT
The Malaysian Soy and Mammographic Density (MiSo) Study is a three-armed, randomized controlled trial with no blinding and no placebo control. Peri- and postmenopausal Malaysian women between 45 and 65 years old were invited to participate in the trial between November 2018 and December 2019 at a private tertiary hospi...
PMC9862880
2.2. Data Collection
A structured questionnaire was used to collect information about participant characteristics at enrolment, including socio-demographic profiles, reproductive factors, physical activity, and medical history. The questions were adapted from a questionnaire previously used in this study population, as described elsewhere ...
PMC9862880
2.3. Intervention and Compliance
Women in the ISF supplement arm were asked to consume 2 soy ISF supplement tablets once daily. Each tablet of the supplement contained 125 mg of soybean (Glycine max) standardized extract that delivered 50 mg of ISFs (consisting of 92% daidzein and 8% genistein in aglycone weight). Women in the ISF diet arm were asked ...
PMC9862880
2.4. Outcome Measurements
The primary outcome in this trial was change in mammographic density (MD) over the study period. Mammography was conducted at enrolment and at Month 12 at the study site, using a single full-field digital mammography machine (Hologic Selenia Mammography System, Hologic Inc., Marlborough, MA, USA). MD was estimated from...
PMC9862880
2.5. Statistical Analysis
within-women
Sample size calculations estimated that a total enrolment of 228 women (76 per arm) were required to detect a 2.5% difference in percent density change between any two arms at 80% power and considering a 5.0% standard deviation [Standard descriptive statistics were used to describe differences across the study arms. Fi...
PMC9862880
3. Results
PMC9862880
3.1. Follow Up during the Study Period
breast cancer
BREAST CANCER
In this randomized controlled trial to investigate the association between soy isoflavone intake and mammographic density as a biomarker of breast cancer risk, 118 women were enrolled and randomized into three study arms (Up to 23% of women were lost in follow up (Importantly, the women who completed the study were sim...
PMC9862880
3.2. Description of Participants in the Primary Analysis
obese or overweight
BREAST CANCER
A total of 90 women were included in the primary analysis (Twelve percent of women reported at least one first degree family member with breast cancer. For many women (65.6%), their last mammogram was more than 2 years ago. Four women reported that this was their first mammogram. Forty-one percent of women were obese o...
PMC9862880
3.3. Change in Mammographic Density over the Study Period
Women in the ISF Supplement arm appeared to have a larger absolute decline in dense area over time, by 1.3 cmWe conducted several sensitivity analyses to test the robustness of our observations. First, limiting the analysis to those who were compliant to the intervention (per-protocol analysis) did not improve the asso...
PMC9862880
3.4. Changes in Mammographic Density over Time
We observed that the decline in MD prior to the intervention, over an average of 5–7 years, appeared to be greater for women in the control arm (−9.4 cm
PMC9862880
3.5. Adverse Events
ADVERSE EVENT
Of the 118 participants who were enrolled and randomized, 62.7% reported at least one adverse event during the study period (
PMC9862880
4. Discussion
within-women, breast cancer
BREAST CANCER
In a randomized controlled trial of 90 healthy peri- and postmenopausal Malaysian women, we found no statistically significant differences in annual MD change for women with or without the soy isoflavone intervention. However, we found that high soy isoflavone intake may benefit women who are perimenopausal or recently...
PMC9862880
5. Conclusions
breast cancer
BREAST CANCER
We demonstrate a plausible causal association between soy isoflavone intake and mammographic density change, as a biomarker of breast cancer risk, among Asian women around or soon after menopause. However, due to the limited sample size in this trial, the findings should be interpreted with caution and require confirma...
PMC9862880
Supplementary Materials
The following supporting information can be downloaded at: Click here for additional data file.
PMC9862880
Author Contributions
P.H.
Conceptualization and methodology: N.R., E.L.M.H., C.H.Y., N.A.M.T., G.L.K., W.K.H., P.H., and S.H.T.; data curation, project administration, and investigation, N.R., B.Y., S.M., L.M.T., H.S., C.H.Y., and E.L.M.H.; formal analysis and validation, N.R., B.Y., S.M., M.E., E.L.M.H., C.H.Y., N.A.M.T., G.L.K., W.K.H., P.H.,...
PMC9862880
Institutional Review Board Statement
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committees and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study protocol and source documents were approved by the Ramsay Sim...
PMC9862880
Informed Consent Statement
Written informed consent was obtained from all participants prior to any study procedures.
PMC9862880
Data Availability Statement
Data can be made available upon reasonable request.
PMC9862880
Conflicts of Interest
The authors declare no conflict of interest.
PMC9862880
ABSTRACT
PMC10089046
Introduction:
ST ELEVATION MYOCARDIAL INFARCTION
Non-ST elevation myocardial infarction is frequently thought to be caused by incomplete blockage of the culprit artery, whereas ST elevation myocardial infarction is frequently thought to be caused by total occlusion of the culprit artery. The objective of the study was to find out the prevalence of occluded coronary a...
PMC10089046
Methods:
-11, COMPLICATIONS
A descriptive cross-sectional study was conducted among non-ST elevation myocardial infarction patients in a tertiary care centre from 22 June 2020 to 21 June 2021 after taking ethical approval from the Institutional Review Committee [Reference number: 4271 (6-11) E2 076/077]. A total of 196 patients were included in t...
PMC10089046
Results:
Among 126 non-ST elevation myocardial infarction patients included in the study, the prevalence of occluded coronary artery was 41 (32.54%) (24.36-40.72, 95% Confidence Interval).
PMC10089046
Conclusions:
The prevalence of occluded coronary arteries was similar to the studies done in similar settings.
PMC10089046
Keywords
PMC10089046
INTRODUCTION
NSTEMI
Non-ST Elevation Myocardial Infarction (NSTEMI) is frequently thought to be caused by incomplete blockage of the culprit artery, whereas STEMI is frequently thought to be caused by total occlusion of the culprit artery.The objective of the study was to find out the prevalence of occluded coronary arteries among non-ST ...
PMC10089046
METHODS
TIMI, NSTEMI, Major branch occlusion, ST-elevation myocardial infarction, stenosis
MYOCARDIAL INFARCTION, LBBB, -11, LEFT BRANCH BUNDLE BLOCK, STENOSIS, COMPLICATIONS, CORONARY ARTERY DISEASE
This was a descriptive cross-sectional study conducted at a tertiary hospital of Manmohan cardiothoracic vascular and transplant centre (MCVTC) with a primary percutaneous coronary intervention (PCI) facility.The patients with ages greater than 18 years old and NSTEMI who underwent coronary angiography from 22 June 202...
PMC10089046
RESULTS
OCA, NSTEMI
DYSLIPIDEMIA
A total of 126 patients were included with the diagnosis of NSTEMI who underwent coronary angiography during the study period. Among 126 NSTEMI patients, the prevalence of occluded coronary arteries (OCA) was 41 (32.54%) (24.36-40.72, 95% CI). However, in patients with OCA, there was female predominance. The mean age o...
PMC10089046
Baseline characteristics of the study population (n= 41).
OCA, Heart failure, NSTEMI
HEART FAILURE, COMPLICATIONS
The mean level of Troponin I was 6.59±12.58. Heart failure developed in 17 (41.46%) of NSTEMI patients with occluded arteries. The in-hospital mortality was 1(2.44%) patient with OCA and the baseline laboratory results and complications developed among patients (
PMC10089046
Biochemical characteristics and in-hospital complications in patients with NSTEMI (n= 41).
TVD, NSTEMI
TVD was also the predominant lesion in NSTEMI with the occluded artery 18 (43.90%). In overall NSTEMI patients culprit artery was as follows: circumflex branch of left coronary artery (LCX) 20 (48.78%), RCA 6 (14.63%) (
PMC10089046
Coronary angiography and interventions in patients with NSTEMI (n= 41).
PMC10089046
DISCUSSION
OCA, NSTEMI, CAD, infarct, dyslipidemia
DIABETES MELLITUS, HYPERTENSION, INFARCT, CAD, DYSLIPIDEMIA
In this study out of 126 patients, 32.50% were NSTEMI with occluded coronary arteries while 67.5% were NSTEMI with non-occluded coronary arteries.In our study, 32.50% of NSTEMI patients had occluded coronary arteries which were similar to previously conducted studies.There was male predominance (59.5%) in our study pre...
PMC10089046
CONCLUSIONS
MYOCARDIAL INFARCTION
The prevalence of occluded coronary arteries was similar to the studies done in similar settings. There is as yet no reliable tool to identify this group of patients before performing angiography. These patients have similar presentations and angiographic findings as ST-segment Elevation myocardial infarction. So wheth...
PMC10089046
Conflict of Interest
PMC10089046
REFERENCES
PMC10089046
Subject terms
DH.Dentin hypersensitivity, DH, pain
COMMON COLD, COLD, DENTIN HYPERSENSITIVITY
The 4-week double-blind clinical trial to manage dentin hypersensitivity (DH) using different desensitizing toothpastes was conducted. 53 participants with DH were enrolled in this trial. The participants were randomized into 3 groups: Group N; no active ingredient-containing toothpaste (Pleasia fluoride-free), Group S...
PMC10066268
Methods
The participants were randomly grouped as: (1) Group N; no active ingredient-containing toothpaste as negative control (Pleasia fluoride-free; Amorepacific, Seoul, Korea), (2) Group SC; a commercially available toothpaste containing strontium chloride (Sensodyne Original; GlaxoSmithKline, Brendtford, UK), (3) Group TP;...
PMC10066268
Sample size determination
The sample size was determined according to the previous trials using G Power
PMC10066268
Inclusion and exclusion criteria
A total of 112 patients volunteered to participate in this study. Prior to enrollment in the clinical trial, a survey was conducted to identify DH, and participants who did not meet the criteria were excluded. Initially, 78 participants (age, 18–65 y) were enrolled and underwent a primary screening assessment prior to ...
PMC10066268
Randomization
HYPERSENSITIVITY
Participants were assigned to each experimental group using a block randomization scheme stratified according to the severity of hypersensitivity. Severity was determined by the average Schiff sensitivity score (mild, 1.167–1.5; moderate: 1.57–1.857, severe: 1.9–2.625) during the screening session. Finally, the 53 part...
PMC10066268
Clinical assessment
JJ
COLD
Patients were assessed at baseline and at 2 and 4 weeks. The assessment was conducted by three authors of the study (JJ, HK and DK). At each assessment, the tooth surface was exposed to three different stimuli: air-blast, cold, and application of an acidic solution. Each stimulus was applied according to a standardized...
PMC10066268
(1) Air-blast
Air was delivered from a standard dental unit air syringe at a distance of approximate 1 cm for 5 s at an operating temperature of 23 °C (±4 °C), directed at the exposed buccal surface of the hypersensitive tooth. The Schiff sensitivity score was used to assess the subject’s response to this stimulus, as follows0 = Sub...
PMC10066268
(2) Cold
RITTER, COLD
Thermal stimuli from the microbrush sprayed immediately with ethyl chloride ice spray (Walter Ritter, Hamburg, Germany) were applied for 1 s to the teeth that had already been tested for air-blast and scored equal to or greater than 1. The Schiff sensitivity score was used to assess the subjects’ response to cold stimu...
PMC10066268
(3) Acid
COLD
A 20% lemon solution (Fior di Limone; Ital Lemon SPA, Lodi, Italy) was used as the acidic stimulus to assess the DH. The solution was applied for 3 s to the identified tooth surface that had already been tested with air-blast and cold using a microbrush at room temperature and scored using Schiff’s sensitivity score.
PMC10066268
(4) VAS
At every visit, participants rated subjective DH of the entire dentition based on VAS, with 0, “None” and 10, “Extremely severe” during the usage of their respective toothpastes. VAS scores were recorded in a case record.
PMC10066268
Safety report
Visual soft-and hard-tissue
ADVERSE EVENTS, CAVITY
Each participant was interviewed regarding the adverse events at each visit. Visual soft-and hard-tissue examinations of the oral cavity were performed at every visit to assess the safety of the products. Spontaneous reports of adverse events were also recorded.
PMC10066268
Statistical analyses
tooth
COLD
The primary outcomes for this study were the Schiff sensitivity scores for air, cold, and acidic stimuli and VAS scores at baseline (0) and at 2 and 4 weeks. For each test group, the Schiff sensitivity score for each stimulus modality was calculated for each patient and tooth at each assessment. Descriptive statistics ...
PMC10066268
Ethics approval
All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This research was performed and reported according to...
PMC10066268
Consent to participate and publish
Informed consent was obtained from all individual participants included in the study.
PMC10066268
Results
PMC10066268
Baseline summary
ALLERGIC REACTIONS
Of the 53 participants enrolled in the study, 2 dropped out due to loss of contact and insistence on allergic reactions; hence, 51 participants completed the study. The study population had a mean age of 32.08 y and a range of 22–65 y. Patient demographics are displayed in Table
PMC10066268
Efficacy assessment
tooth
COLD
This study was sufficiently powered (1-β = 0.94) to demonstrate the clinical equivalence of group SC and TP. They were significantly different from group N in the aspect of the reduction of Schiff sensitivity score. A mixed-effects model was used for statistical analysis with adjustments for age, sex, and tooth positio...
PMC10066268
(1) Air-blast
The reduction in air Schiff sensitivity scores of Group TP at 4 weeks from baseline was significantly greater than the reduction in scores of group N (p = 0.0002) (Table Statistics of the Schiff sensitivity score and post-hoc analysis of the mixed effect model for repeated data [mixed effect model; LS mean and 95% CI]....
PMC10066268
(2) Cold
COLD
The Group TP exhibited a significantly higher efficacy of desensitization to cold stimuli than the N group (p = 0.0205). There was no significant difference between Groups TP and SC (p = 0.6944) and Groups SC and N (p = 0.4782).
PMC10066268
(3) Acid
There were no significant differences among the three groups in terms of the alleviating effects of acidic sensitivity. However, for acidic stimuli, all groups showed a time-dependent decrease in the Schiff sensitivity score from baseline (2 weeks, p = 0.0159; 4 weeks, p < 0.0001).
PMC10066268
(4) VAS
The mean VAS scores at each follow-up are shown in Table
PMC10066268
Safety reports
allergic lesion, aphthous, traumatic
Over the 4-week follow-up period, soft tissue abnormalities which was not presented at baseline were reported by one participant in group SC. After thorough clinical examination and photographic evaluation, the patient consulted a specialist in oral internal medicine. The lesion was localized on the right side of the t...
PMC10066268
Discussion
COLD, TOOTH SENSITIVITY
To relieve DH, various desensitizing modalities have been used at home or professionally applied. Toothpaste is an important agent for the relief of DH. The first desensitizing toothpastes claimed to either occlude dentinal tubules (those that contained strontium salts and fluorides) or destroy vital components within ...
PMC10066268
Acknowledgements
This study was funded from Osstem Implant Co., LTD (Seoul, Korea). The author would like to thank to Dr. Su-Jin Jung, statistician of Kyung Hee Medical Center, for analyzing the statistics of this study.
PMC10066268
Author contributions
All authors contributed to the study conception and design. Data collections were performed by J.-H. J., H.-J. K. and D.-S. K. Data analysis was performed by S. O. The first draft of the manuscript was written by J.-H. J. and S. O. and all authors commented on previous versions of the manuscript. All authors read and a...
PMC10066268
Data availability
The datasets generated and analyzed during the current study are available in patients’ records attending the Conservative Dentistry Department, Kyung Hee University Dental Hospital. The datasets used and/or analyzed during this study are available from the corresponding author on reasonable request and also with the p...
PMC10066268
Competing interests
The authors declare no competing interests.
PMC10066268
References
PMC10066268
Subject terms
BLOOD
Although weekend recovery sleep is common, the physiological responses to weekend recovery sleep are not fully elucidated. Identifying molecular biomarkers that represent adequate versus insufficient sleep could help advance our understanding of weekend recovery sleep. Here, we identified potential molecular biomarkers...
PMC10689438
Introduction
SECONDARY
In the United States, more than one-third of adults report sleeping less than the recommended seven hours per night and 30% report sleeping less than six hours per nightRecent advances in machine learning and omics technologies, including metabolomics, have enhanced the biomarker discovery and development pipeline and ...
PMC10689438
Materials and methods
PMC10689438
Participants
All study procedures were approved by the Colorado Clinical and Translational Sciences Institute, the Colorado Multiple Institutional Review Board (IRB), and the University of Colorado Boulder IRB, and were conducted in accordance to the Declaration of Helsinki. All participants signed the informed consent prior to ini...
PMC10689438
Untargeted metabolomics
Methods for sample preparation, liquid chromatography, mass spectrometry, and data extraction were conducted similar to our previous work and described in Supplementary Material
PMC10689438
Compound annotation
First, for all compounds in the dataset we used Mass Profiler Professional (v.B.14.5; Agilent Technologies, Inc.) to putatively annotate common chemical names based on mass and isotope ratios with an error window of < 10 ppm. In this workflow, compounds are first searched against an in-house database of authentic stand...
PMC10689438
Compound selection for biomarker model development
We detected a total of 3596 compounds. To identify the compounds that most effectively distinguish between the CON (9h per night sleep opportunities) versus SR (5h per night sleep opportunities) groups, we applied a random forest (RF) algorithm. We chose RF for its ability to handle and integrate such a high number of ...
PMC10689438
Biomarker model building
Machine learning models perform differently based on the dataset and datatype they are applied toSchematic representation of the workflow used for biomarker algorithm development. Black sample indicators represent the CON group. Red sample indicators represent the SR group. Blue sample indicators represent the WR group...
PMC10689438
Performance metrics for biomarker models
Our objective was to build a balanced model capable of effectively distinguishing samples from participants in the SR group versus the CON group. Given the early stage of this research, we aimed for a model that equally prioritized sensitivity and specificity, which helps minimize bias from unbalanced sample sizes. A c...
PMC10689438
Machine learning voting ensemble
Prior data shows combining machine learning models, called ensemble methods, can produce better classifiers than single models and their use in biomedical science is increasing
PMC10689438
Biomarker model testing in the weekend recovery group
Because the ensemble method produced the highest overall G-Mean, it was used to classify the WR samples (Fig. WR samples classification by a voting ensemble algorithm. WR, insufficient sleep with weekend recovery sleep group; ML, machine learning; WR-Adequate, samples from WR group scored as adequate sleep by ML ensemb...
PMC10689438
Results
INSULIN SENSITIVITY
The published primary findings from this study were focused on the effect of weekend recovery sleep on metabolic health outcomes including insulin sensitivity
PMC10689438
Top 25 compounds that differentiate adequate versus insufficient sleep
Out of the top 25 compounds identified as most important to differentiate samples from the CON group versus SR group (Fig. Principal Components Analysis of the SR and CON samples using the top 25 compounds. (The loadings plot (Fig. 
PMC10689438
Biomarker model performance
G-mean values, sensitivity, and specificity from the 8 machine learning algorithms are represented in Fig. G-mean, sensitivity and specificity for each machine learning algorithm trained and tested on sample from the CON and SR groups.The four algorithms with the highest G-means (glmnet, knn, rf, svm) were selected to ...
PMC10689438
Classification of samples from the WR group
When the ensemble algorithm was applied to samples from the WR group, 22 (55%) samples were classified as adequate sleep (WR-ADEQUATE) and 18 (45%) samples were classified as insufficient sleep (WR-INSUFFICIENT).The PCA representation (Fig. Principal component analysis of the CON, SR, and WR samples. The color of sampl...
PMC10689438
Discussion
We used data from a rigorous randomized controlled trial to determine if a blood metabolomics-based biomarker can distinguish between participants that received a week of adequate sleep versus a week of insufficient sleep. We also examined the impact of a weekend of recovery sleep on our top-performing biomarker. Our f...
PMC10689438
Supplementary Information
The online version contains supplementary material available at 10.1038/s41598-023-48208-z.
PMC10689438
Acknowledgements
WRIGHT
We thank the study participants, the University Colorado Boulder Clinical Translational Research Center staff, and B. Smith, B. Brainard, B. Griffin, T. Dear, A. McHill, T. Moehlman, E. Stothard, and G. Wright, for study assistance.
PMC10689438