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Acknowledgments | The authors thank all the participants in the study. The authors also thank all research nurses and physicians at the sites, as well as Ingela Johansson, Gosia Smolinska and Claudia Matzke for skillful laboratory work. The authors are grateful to Dr. Joachim Davidsson (Department of Radiology, Linköping University Hosp... | PMC9933867 | ||
Conflict of interest | The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. | PMC9933867 | ||
Publisher’s note | All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or ... | PMC9933867 | ||
Supplementary material | The Supplementary Material for this article can be found online at: Click here for additional data file. | PMC9933867 | ||
References | PMC9933867 | |||
Subject terms | Artificial intelligence (AI) has been developed for echocardiographyThe impact of artificial intelligence in cardiac function assessment is evaluated by a blinded, randomized non-inferiority trial of artificial intelligence versus sonographer initial assessment of the left ventricular ejection fraction. | PMC10115627 | ||
Main | DISEASE | Accurate quantification of cardiac function is necessary for disease diagnosis, risk stratification and assessment of treatment responseClinical practice guidelines recommend when assessing LVEF based on cardiac imaging—most commonly echocardiography—that the measurements should be performed repeatedly over multiple ca... | PMC10115627 | |
Cohort characteristics | We enroled 3,769 transthoracic echocardiogram studies originally performed at an academic medical centre between 1 June 2019 and 8 August 2019; these studies were prospectively re-evaluated by 25 cardiac sonographers (mean of 14.1 years of practice) and 10 cardiologists (mean of 12.7 years of practice). In total, 3,495... | PMC10115627 | ||
Assessment of blinding | BANG | After completing each study, cardiologists were asked to predict the agent of initial interpretation. Cardiologists correctly predicted the method of initial assessment for 1,130 (32.3%) studies, incorrectly guessed for 845 (24.2%) studies and were unsure whether initial assessment was provided by AI or sonographers fo... | PMC10115627 | |
Consort diagram. | Screening, randomization and follow-up. | PMC10115627 | ||
Secondary safety outcome | SECONDARY | The secondary safety outcome of substantial difference between final cardiologist-adjudicated LVEF compared with the previously clinically reported LVEF occurred in 871 (50.1%) studies in the AI group compared with 957 (54.5%) studies in the sonographer group (difference of −4.5%, 95% confidence interval: −7.8% to −1.2... | PMC10115627 | |
Other outcomes and subgroup analyses | The reduction in the primary end point with the AI group was consistent across all major subgroups (Table | PMC10115627 | ||
Comparison of AI versus sonographer guidance on cardiologist assessment and difference between final versus previous cardiologist assessments. | Dots represent individual studies and lines represent the lines of best fit. MAD, mean absolute difference.We additionally assessed the frequency of changes from initial to final assessment crossing a clinically meaningful threshold (that is, LVEF of 35% for consideration of implantable defibrillator therapy) post-hoc.... | PMC10115627 | ||
Discussion | In this trial of board-certified cardiologists adjudicating clinical transthoracic echocardiographic exams, AI-guided initial evaluation of LVEF was found to be non-inferior and even superior to sonographer-guided initial evaluation. After blinded review of AI versus sonographer-guided LVEF assessment, cardiologists we... | PMC10115627 | ||
Methods | PMC10115627 | |||
Study design and oversight | Cardiologists with board certification in echocardiography were assigned to read independent transthoracic echocardiogram studies randomized to initial assessment by AI versus sonographer. Imaging studies were initially acquired and interpreted clinically by a board-certified cardiologist between 1 June 2019 and 8 Augu... | PMC10115627 | ||
Model design and clinical integration | The architecture and design of the AI model have been previously describedFor both sonographers and cardiologists, the entire study (most often between 60 and 120 videos) was shown in the standard clinical reporting software. The study was shown without any annotations to the sonographer, who chose the apical-4-chamber... | PMC10115627 | ||
Outcomes assessment | SECONDARY | The primary outcome was the change in LVEF between the initial assessment by AI or sonographer and the final cardiologist assessment. The primary outcome was evaluated both as the proportion of studies with substantial change and the mean absolute difference between initial and final assessments. Substantial change was... | PMC10115627 | |
Statistical analysis | SECONDARY | The trial was designed to test for non-inferiority, with a secondary objective of testing for superiority with respect to the primary end point. Non-inferiority is shown if the lower limit of the 95% confidence interval for the between-group difference in the primary end point was less than 5% (less than the natural va... | PMC10115627 | |
Reporting summary | Further information on research design is available in the | PMC10115627 | ||
Online content | Any methods, additional references, Nature Portfolio reporting summaries, source data, extended data, supplementary information, acknowledgements, peer review information; details of author contributions and competing interests; and statements of data and code availability are available at 10.1038/s41586-023-05947-3. | PMC10115627 | ||
Supplementary information | The online version contains supplementary material available at 10.1038/s41586-023-05947-3. | PMC10115627 | ||
Acknowledgements | No external funding was obtained for this study. We thank the Cedars-Sinai Medical Center Enterprise Information Systems Enterprise Imaging team for their support with clinical integration and deployment. | PMC10115627 | ||
Author contributions | B.H., S.C., J.Y.Z. and D.O. designed the clinical trial, study protocol and implementation of the AI model. B.H., G.D. and M.J. engineered technical design and clinical deployment. A.C.K., J.H.C., N.Y., C.P., T.S., J.E., N.A.B., J.W., K.J. and R.S. performed the blinded review of AI versus sonographer assessments. B.H.... | PMC10115627 | ||
Peer review | PMC10115627 | |||
Data availability | The AI model was trained using echocardiogram videos from Stanford Healthcare following Stanford IRB protocol 43721 with waiver of individual consent. A set of de-identified Stanford Healthcare echocardiogram videos is publicly available at EchoNet-Dynamic ( | PMC10115627 | ||
Code availability | The code for the AI model is available at GitHub ( | PMC10115627 | ||
Competing interests | Stanford University is in the process of applying for a patent application covering video-based deep learning models for assessing cardiac function that lists B.H., J.Y.Z. and D.O. as inventors | PMC10115627 | ||
References | PMC10115627 | |||
Purpose | The purpose of this study was to investigate the potential of a doubled semitendinosus (ST) and a single gracilis tendon (GT) lateral meniscus autograft to restore the knee joint kinematics and tibiofemoral contact after total lateral meniscectomy (LMM). | PMC10276070 | ||
Methods | knee joints | Fourteen human knee joints were tested intact, after LMM and after ST and GT meniscus autograft treatment under an axial load of 200 N during full range of motion (0°–120°) and four randomised loading situations: without external moments, external rotation, valgus stress and a combination of external rotation and valgu... | PMC10276070 | |
Results | knee joints | LMM led to significant rotational instability of the knee joints ( | PMC10276070 | |
Conclusion | The doubled ST lateral meniscus autograft improved the knee joint kinematics significantly and restored the tibiofemoral contact mechanics almost comparable to the native situation. Thus, from a biomechanical point of view, ST meniscus autografts might be a potential treatment alternative for patients who are indicated... | PMC10276070 | ||
Supplementary Information | The online version contains supplementary material available at 10.1007/s00167-022-07300-z. | PMC10276070 | ||
Keywords | Open Access funding enabled and organized by Projekt DEAL. | PMC10276070 | ||
Introduction | Meniscal injuries are among the most common injuries within the knee joint [ | PMC10276070 | ||
Materials and methods | knee joints | Following IRB approval (No. 37/20; University of Ulm), fourteen non-osteoarthritic fresh frozen cadaveric knees (11 males, 3 females; all left knees; median age 57 years, range 28–64 years; Science Care, Phoenix, AZ, USA) were thawed at room temperature and both the gracilis tendon (GT) and ST were harvested following ... | PMC10276070 | |
Biomechanical testing | An established knee joint loading simulator [ | PMC10276070 | ||
Statistical analysis | On the basis of a comparable study [ | PMC10276070 | ||
Results | PMC10276070 | |||
Joint kinematics | varus-valgus | Compared to the native condition, the other knee joint conditions (LMM, GT, ST) did not affect the varus-valgus rotation, except for the LMM state at 90° flexion (Box plots (minimum, maximum, median, 25th and 75th percentile values) of | PMC10276070 | |
Lateral tibiofemoral contact mechanics | In the native knee joint, the lateral CPMinimum, median and maximum peak contact pressure (CPStatistically different to bold numbers within one loading condition and the according flexion angleNon-parametric statistical analyses: Minimum, median and maximum mean contact pressure (CPStatistically different to bold numbe... | PMC10276070 | ||
Discussion | knee flexion [A | The most important finding of this biomechanical in vitro study is that the ST meniscus autograft was able to significantly improve both the joint kinematics and the tibiofemoral contact parameters after LMM. To the best of the authors’ knowledge, this is the first study investigating the kinematic knee joint changes a... | PMC10276070 | |
Conclusion | The doubled ST lateral meniscus autograft improved the knee joint kinematics significantly and restored the tibiofemoral contact mechanics almost comparable to the native situation. Thus, from a biomechanical point of view, ST meniscus autografts might be a potential treatment alternative for patients who are indicated... | PMC10276070 | ||
Supplementary Information | Below is the link to the electronic supplementary material.Supplementary file1 (XLSX 35 KB)Supplementary file2 (XLSX 35 KB)Supplementary file3 (XLSX 27 KB)Supplementary file4 (XLSX 34 KB)Supplementary file5 (XLSX 34 KB)Supplementary file6 (PDF 529 KB)Supplementary file7 (DOCX 21 KB)Supplementary file8 (DOCX 21 KB) | PMC10276070 | ||
Acknowledgements | The authors acknowledge Patrizia Horny from the Institute of Orthopaedic Research and Biomechanics Ulm for her art design support. | PMC10276070 | ||
Author contributions | AMS | JL and TK performed the specimen preparation and the surgical interventions. AMS, JL and TK performed the joint simulator tests. JS performed the equilibration and calibration of the pressure sensors. JS performed the data extraction and conducted the statistical analyses. AMS drafted the manuscript. AI, HR and TK supp... | PMC10276070 | |
Funding | Open Access funding enabled and organized by Projekt DEAL. This study was funded by the Deutsche Arthrose-Hilfe e.V. (P507). | PMC10276070 | ||
Data availability | All data generated or analysed during this study are included in this published article (and its supplementary information files). | PMC10276070 | ||
Declarations | PMC10276070 | |||
Conflict of interest | The authors declare that they have no competing interests. | PMC10276070 | ||
Ethical approval | The study design was approved by the institutional review board of the University of Ulm under reference number 37/20. | PMC10276070 | ||
Informed consent | No informed consent was required for this study. | PMC10276070 | ||
References | PMC10276070 | |||
ABSTRACT | PMC9924963 | |||
Purpose | metabolic syndrome, SB | METABOLIC SYNDROME, INSULIN SENSITIVITY | This study aimed to investigate whether a reduction in daily sedentary behavior (SB) improves insulin sensitivity in adults with metabolic syndrome in 6 months, without adding intentional exercise training. | PMC9924963 |
Methods | overweight and metabolic syndrome | Sixty-four sedentary inactive middle-age adults with overweight and metabolic syndrome (mean (SD) age, 58 (7) yr; mean (SD) body mass index, 31.6 (4.3) kg·m | PMC9924963 | |
Results | SB decreased by 40 (95% confidence interval, 17–65) min·d | PMC9924963 | ||
Conclusions | weight loss | ADIPOSITY, INSULIN SENSITIVITY | An intervention aimed at reducing daily SB resulted in slightly decreased fasting insulin, but had no effects on insulin sensitivity or body adiposity. However, as the change in insulin sensitivity associated with the changes in SB and body mass, multifaceted interventions targeting to weight loss are likely to be bene... | PMC9924963 |
Key Words | SB, MetS, premature death, cluster of metabolic disorders, metabolic disorders | DISORDER, METABOLIC SYNDROME, CARDIOVASCULAR DISEASES, INSULIN RESISTANCE, METABOLIC DISORDERS, INSULIN RESISTANCE, TYPE 2 DIABETES | The associations between measured sedentary behavior (SB) and metabolic disorders as well as premature death are well established (Metabolic syndrome (MetS) is a lifestyle-related cluster of metabolic disorders that are associated with a sedentary lifestyle and a positive energy balance and can lead to type 2 diabetes ... | PMC9924963 |
MATERIALS AND METHODS | This study was a randomized controlled trial in free-living conditions. The study was conducted at the Turku PET Centre, Turku, Finland, between April 2017 and March 2020 according to good clinical practice and the Declaration of Helsinki. The participants gave their informed consent before entering the study. The stud... | PMC9924963 | ||
Study participants | The participants were recruited from the local community by newspaper advertisements and bulletin leaflets. The inclusion criteria for choosing the participants were as follows: age of 40–65 yr, body mass index (BMI) of 25–40 kg·m | PMC9924963 | ||
Anthropometric and metabolic measurements | MetS, fat-free mass | BLOOD, CREST | HEC was performed as previously described by Sjöros et al. (Venous blood samples were drawn after at least 10 h of fasting and analyzed at the Turku University Hospital Laboratory. Plasma insulin was determined by electrochemiluminescence immunoassay (Cobas 8000 e801; Roche Diagnostics GmbH, Mannheim, Germany). Plasma ... | PMC9924963 |
Accelerometry | APE | SB and PA were measured during waking hours through the whole intervention with a hip-worn triaxial accelerometer (Movesense; Suunto, Vantaa, Finland) with embedded measurement and analysis algorithms (ExSed; UKK Institute, Tampere, Finland). The baseline SB and PA were measured for 4 wk at the screening phase with a h... | PMC9924963 | |
Intervention | After the baseline measurements, the participants were randomly allocated by a statistician to the INT and CONT groups using random permuted blocks with 1:1 allocation ratio and block size of 44, performed separately for men and women.The participants in the INT group received a 1-h tailored personal counseling session... | PMC9924963 | ||
Statistical methods | The sample size was determined according to the following power calculations: Based on the earlier finding that GU was increased by 2.4 μmol·kg | PMC9924963 | ||
Additional analyses | We ran additional analyses by dividing the participants into two groups according to the changes in measured SB as a proportion of the daily wear time of the accelerometer. The participants who reduced their daily SB by at least three percentage points compared with the baseline (that equals about a 27-min reduction in... | PMC9924963 | ||
RESULTS | In total, 263 individuals volunteered, of which 155 participated in the screening measurements and 64 participants were included (Fig. S1, Supplemental Digital Content, Study flow diagram, Study participant characteristics at the baseline.Unless otherwise stated, the results are presented as mean (SD). The differences ... | PMC9924963 | ||
Accelerometry | The mean (SD) duration of the intervention was 171 (36) d. Accelerometer data of 56 participants were successfully collected during the intervention with a median (Q1, Q3) duration of 117 (74, 142) d. The data collection of eight participants failed, one because of discontinued participation in the study and seven beca... | PMC9924963 | ||
Anthropometric and metabolic outcomes | MetS | INSULIN SENSITIVITY | Body mass, BMI, and waist circumference decreased similarly in both groups (Fig. Anthropometric results of the intervention (Metabolic results of the intervention (Energy intake of the intervention (The change in insulin sensitivity was inversely associated with the changes in MetS score, BMI, body mass, fasting glucos... | PMC9924963 |
Additional analyses | INSULIN SENSITIVITY | When the participants were divided into two groups according to the changes in accelerometer-measured SB, insulin sensitivity increased in the more active group compared with the continuously sedentary group (Fig. Whole-body insulin-stimulated GU (M-value) measured by HEC in more active (accelerometer-measured SB decre... | PMC9924963 | |
DISCUSSION | In this study, a tailored intervention aimed to reduce SB by 1 h·d | PMC9924963 | ||
Insulin resistance | tissue damage, hyperinsulinemia | INSULIN RESISTANCE, HYPERINSULINEMIA | Insulin resistance is currently considered a protective mechanism against hyperglycemia-induced hyperinsulinemia in plasma and subsequent hyperglycemia-induced tissue damage ( | PMC9924963 |
Behavior change | This intervention was successful in reducing SB, but the mean change during the intervention (40 min·dThe intervention aimed at replacing SB with standing and nonexercise PA, but during the whole 6-month intervention, the participants were able to sustain only the increase in MVPA (consisting mainly of moderate-intensi... | PMC9924963 | ||
Effectiveness of replacing SB with PA in daily activities | overweight | INSULIN SENSITIVITY | Even if the amount of MVPA and step count significantly increased, the intervention was unable to enhance whole-body insulin sensitivity measured by HEC. The (nearly total) lack of VPA may be the reason that MVPA was not effective in improving insulin sensitivity in this study. It is possible that VPA rather than moder... | PMC9924963 |
Methodological consideration | In some studies, metabolic markers or physical functioning have modestly improved even if no changes in device-measured SB were detected at the end of the intervention ( | PMC9924963 | ||
Strengths and limitations | weight loss | INSULIN SENSITIVITY | Key strengths of this study are the randomized controlled trial design, gold standard method for measuring whole-body insulin sensitivity, and the 6-month assessment of SB and PA by accelerometry. A limitation was that because of the nature of the intervention, blinding of the participants was not possible. Moreover, t... | PMC9924963 |
Clinical implications | Insulin sensitivity is a multifactorial phenomenon, and therefore, multifactorial lifestyle interventions with sufficient support and follow-up strategies can be expected to be successful ( | PMC9924963 | ||
CONCLUSIONS | MetS | INSULIN SENSITIVITY | Reducing 40 min of daily SB mainly by adding nonexercise PA seems not to be enough to improve whole-body insulin sensitivity in adults with MetS in 6 months, although it minimally decreased fasting insulin. Instead, multifaceted approaches with sustained changes in SB and PA behaviors including exercise and a healthy d... | PMC9924963 |
Supplementary Material | PMC9924963 | |||
SUPPLEMENTARY MATERIAL | Diabetes | DIABETES | The authors thank the staff in the Turku PET Centre, University of Turku, and the laboratory personnel in the Turku University Hospital Laboratory for their proficient assistance in conducting the study. This study was conducted within the Centre of Excellence in Cardiovascular and Metabolic Research, supported by the ... | PMC9924963 |
REFERENCES | PMC9924963 | |||
1. Introduction | hypoxia, FiOAltitude/hypoxic, infections, injuries | HYPOXIC, HYPOXIA, INFECTIONS | The aim of this study was to evaluate the effects of D-aspartic acid (DAA) supplementation during a simulated altitude protocol on the hormonal and hematological responses in athletes. We hypothesized that DAA supplementation would contribute to an increase in the luteinizing hormone (LH), free, and testosterone and a ... | PMC10780457 |
2. Materials and Methods | PMC10780457 | |||
2.1. Study Participants | This study involved 16 young men (aged 18 to 25 years) participating in competitive, Olympic-style boxing. The inclusion criteria required a minimum of a six-month washout period from previous altitude/hypoxic training and baseline blood testosterone levels within the age-specific reference range.The participants were ... | PMC10780457 | ||
2.2. Study Design | hypoxia | HYPOXIA | The experiment consisted of four study series (S1 to S4). S1 involved baseline tests before the start of supplementation and LH–TL training. S2 took place after the fourth day of supplementation and after the first night of exposure to hypoxia. S3 was conducted after the ninth day of supplementation and after the sixth... | PMC10780457 |
2.3. DAA Supplementation | hypoxia | HYPOXIA | During this study, the participants in the DAA group took 6 g/day of DAA in the form of gelatin capsules for 14 days. The dose was divided into equal portions and administered twice a day at similar intervals. In turn, participants in the C group received a placebo (cellulose) in identical gelatin capsules, with the do... | PMC10780457 |
2.4. LH–TL Protocol and Conditioning Training | hypoxia | HYPOXIA | During this study, both DAA and C participants were subjected to continuous hypoxia for 10–12 h a day over a period of 11 days. In the rooms where the participants stayed in the evening and at night, the fraction of inspired oxygen (FiOThe training program consisted of two basic microcycles (weeks) with progressively i... | PMC10780457 |
2.5. Diet during the Experiment | dehydration | DEHYDRATION | As mentioned above, throughout the experiment, all athletes lived at the same accommodation and followed the same training schedule, sleeping time, and diet. During the experiments, the participants consumed a controlled mixed diet (50% CHO, 20% Fat, 30% Pro). Daily energy intake was set at 3500–4000 kcal (depending on... | PMC10780457 |
2.6. Statistical Analysis | The results of the experiment were analyzed using StatSoft Statistica 13.0 software. The results are presented as arithmetic means (x) with standard deviations (SD). The Lilliefors test was used to demonstrate the consistency of the results with normal distribution. The intergroup differences between consecutive resear... | PMC10780457 | ||
3. Results | PMC10780457 | |||
3.1. Hormonal Response | The analysis of variance (ANOVA) showed no statistically significant group × training interactions for changes in resting values of T, fT, C, or LH following DAA supplementation compared to the control group. However, ANOVA revealed a statistically significant effect of training on changes in T levels (F = 12.572, | PMC10780457 | ||
3.2. Hematological Response | The statistical analysis showed no significant group × training interactions for changes in resting values of red blood cell count (RBC), hemoglobin concentration (HGB), hematocrit (HCT), or blood reticulocyte percentage (Ret) following DAA supplementation compared to the control group ( | PMC10780457 | ||
3.3. Training Loads and Changes in Blood Creatine Kinase (CK) Activity | TSS | The statistical analysis showed no significant differences in training load (TSS; 2038 ± 54—DAA group vs. 2068 ± 43—C group) in the study groups. Additionally, ANOVA showed no statistically significant group × training interactions for changes in CK activity in the blood during the experiment. However, ANOVA revealed a... | PMC10780457 | |
4. Discussion | hypoxia, fatigue | HYPOXIC, HYPOXIA | A high T blood concentration and a favorable T/C ratio are considered important factors influencing the effectiveness of altitude training [The results of our study showed that a 2-week DAA supplemental protocol (6 g per day) did not cause significant beneficial changes in blood testosterone (T, fT) concentration durin... | PMC10780457 |
5. Study Limitations | hypoxia, ’ | HYPOXIA | To the best of our knowledge, our study is the first in which the effect of DAA supplementation was assessed in normobaric hypoxia during the LH–TL protocol. Our experiment, however, is not without certain limitations. Firstly, we did not measure the levels of the analyzed indicators immediately before the initial expo... | PMC10780457 |
Author Contributions | Conceptualization: K.P. and M.C.; methodology: K.P., M.C. and R.G.; investigation: K.P., M.C. and R.G.; database collection: K.P., M.C. and A.Z.; statistical analysis: K.P. and M.C.; writing—original draft: K.P. and M.C.; writing—review and editing: K.P., M.C., A.Z. and R.G.; resources: K.P., M.C. and R.G.; funding acq... | PMC10780457 | ||
Institutional Review Board Statement | POLAND | This study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Ethics Committee of the Institute of Sport—National Research Institute in Warsaw, Poland (No. KEBN-22-73-KP, 2 November 2022). | PMC10780457 | |
Informed Consent Statement | Informed consent was obtained from all subjects involved in this study. | PMC10780457 | ||
Data Availability Statement | The data presented in this study are available upon request from the corresponding author. The data are not publicly available due to privacy. | PMC10780457 |
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