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| ID | Type | Description | Link |
|---|---|---|---|
| P20GM113125 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of General Medical Sciences (NIGMS) | NIH |
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This study will focus on improving brain health through dietary modification of added sugars in middle aged adults (50- 64 years old). Participants will be fed two 10-day diets (one diet containing 5% of total energy from added sugars and one diet containing 25% of total energy from added sugars) and examine blood vessel function, hippocampus structure using a MRI, and memory performance.
Aging is the primary risk factor for Alzheimer's disease (AD) which is the most common form of dementia and among the fastest growing causes of morbidity and mortality in the United States. The risk factors for AD emerge during midlife and are similar to cardiovascular and cerebrovascular diseases. The impact of midlife peripheral vascular changes on cardiovascular risk are worsened by poor lifestyle habits, including eating a diet that contains a lot of added sugars (defined as all caloric sweeteners added to food during processing or preparation). One effect of eating a high added sugar diet is an elevation in blood triglycerides (TGs), which impairs blood vessel function by causing inflammation; however, it is not known whether eating a lot of added sugars affects the blood vessels in the brain. The purpose of this project is to determine if there is a link between added sugar intake and brain health in midlife adults. Our hypothesis is that eating excess added sugar impairs the structure and function of an area of the brain called the hippocampus by increasing plasma TGs and systemic inflammation. To test this, we will have people eat a high and low sugar diet for 10 days each (in a random order) and test how each diet affects their blood vessel function, the structure of their hippocampus, and their memory performance. We expect to show that eating a diet that contains a lot of added sugars worsens brain health compared to a diet that contains few added sugars. The data generated from this project will help us better understand risk factors for dementia and will be used to support a future grant proposal to the National Institutes of Health aimed at lowering added sugar intake in mid-life adults and individuals with mild cognitive impairment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Low Added Sugar Diet | Experimental | Subjects will be provided with a diet that is low in added sugars. |
|
| High Added Sugar Diet | Experimental | Subjects will be provided with a diet that is high in added sugars. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Low Added Sugar Diet | Other | Consumption of 10 days of a diet low in added sugars (5% of total caloric intake) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Arterial Compliance (m^2 Kilopascal^-1) | Change in cross-sectional area of the common carotid artery (assessed using ultrasound) per 1 mmHg increase in carotid artery blood pressure (assessed by applanation tonometry). A lower carotid artery compliance is indicative of stiffer elastic arteries. | Day 10 of the diet |
| Cerebrovascular Reactivity (Percent Increase in Cerebral Perfusion Normalized to the Increase in PETCO2 | Cerebrovascular reactivity (CVR) is the relative (percent) change in total cerebral perfusion measured using pseudo-continuous arterial spin labeling per mmHg change in end-tidal carbon dioxide (ETCO2) during a brief period of hypercapnia. Hypercapnia was induced by prospective end-tidal targeting (RespirAct, Thornhill Medical) in which a target change in end-tidal CO2 of +9 millimeters of mercury (mmHg) was set. Data were only analyzed if ETCO2 changed by at least 6.5 mmHg. All data were then normalized to the absolute change in ETCO2. | Day 10 of the diet |
| Hippocampal Stiffness (kPa) | Noninvasive brain imaging using Magnetic Resonance Elastography (MRE) to estimate tissue mechanical properties. Stiffness values are derived from the propagation of shear waves delivered to the head using vibration at 50 Hertz (Hz) from an acoustic driver system (Resoundant, Inc, Rochester MN) and reflects the distribution and organization of neurons, axons, and glial cells. A higher brain stiffness indicates greater tissue integrity. A nonlinear inversion algorithm estimated mechanical properties in the brain from acquired MRE displacement data to map shear modulus, G = G'+iG", where G' is the storage modulus and G'' is the loss modulus. From these parameters, stiffness is calculated, μ = 2*|G|^2 / (|G|+G') | Day 10 of the diet |
| Hippocampal Damping Ratio (Unitless Ratio) | Noninvasive brain imaging using Magnetic Resonance Elastography (MRE) to estimate tissue mechanical properties. Damping Ratio is derived from the propagation of shear waves delivered to the head using vibration at 50Hz from an acoustic driver system (Resoundant, Inc, Rochester MN) and reflects the relative elasticity of the brain tissue. A lower damping ratio indicates greater tissue integrity. A nonlinear inversion algorithm estimated mechanical properties in the brain from acquired MRE displacement data to map shear modulus, G = G'+iG", where G' is the storage modulus and G'' is the loss modulus. From these parameters, damping ratio is calculated, ξ = G"/2*G' |
| Measure | Description | Time Frame |
|---|---|---|
| Carotid-femoral Pulse Wave Velocity (CFPWV) (m/Seconds) | Carotid-femoral pulse wave velocity (CFPWV) assessed using applanation tonometry of the carotid artery and cuff-based assessment of the femoral pulse wave (SphygmoCor XCEL). CFPWV is calculated as the distance between the carotid and femoral pulse divided by the time-delay between pulses. A higher CFPWV is indicative of stiffer elastic arteries. |
| Measure | Description | Time Frame |
|---|---|---|
| Inflammatory Cytokines (%) | Biomarkers of inflammation (e.g. cytokines) from peripheral blood mononuclear cells | Day 10 of the diet |
| Sleep Quality (%) | Sleep quality will be continuously measured for 10 days using an Actiwatch. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Christopher Martens, Ph.D. | University of Delaware | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Delaware | Newark | Delaware | 19713 | United States |
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44 participants were consented and randomized. After baseline testing, but prior to starting the intervention, 5 participants withdrew [MRI concerns (N=3) or unable to maintain the required time commitment (N=2)]. 1 participant started the intervention, but was dropped due to a change in medication not-related to the study, thus making this participant ineligible. A total of 38 participants completed both the high and low sugar diet, with a ≥ 2-week washout in between.
Participants were screened for inclusion in this study at the University of Delaware between January 11, 2022 - January 5, 2024. The study concluded on May 3, 2024.
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| ID | Title | Description |
|---|---|---|
| FG000 | Low Sugar, High Sugar Diet | Subjects will be provided with a diet that is low in added sugars followed by a diet that is high in added sugars.
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| FG001 | High Sugar, Low Sugar Diet | Subjects will be provided with a diet that is high in added sugars followed by a diet that is low in added sugars.
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| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Low Sugar, High Sugar Diet | Subjects will be provided with a diet that is low in added sugars followed by a diet that is high in added sugars.
|
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Arterial Compliance (m^2 Kilopascal^-1) | Change in cross-sectional area of the common carotid artery (assessed using ultrasound) per 1 mmHg increase in carotid artery blood pressure (assessed by applanation tonometry). A lower carotid artery compliance is indicative of stiffer elastic arteries. | Posted | Mean | Standard Deviation | m^2 kilopascal^-1 | Day 10 of the diet |
|
The study took place from 01/11/2022 to 05/03/2024, (e.g., 2 year, 5 months). Adverse events were monitored from baseline test to end of intervention period (completion of 10-day high and 10-day low sugar diet, including monitoring over the washout period). On average, adverse events were monitored for a total of 111 days. On average, it took 38 days to start the first diet after baseline testing. On average, the washout period was 53 days.
The study contain minimal risk and all participants were considered healthy (free of disease).
This study was a crossover design, in which participants completed the diet order as 1). low-sugar diet 2). high-sugar diet -or- 1). high-sugar diet 2). low-sugar diet.
Adverse events are reported per diet in all participants.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Low Sugar Diet | Subjects will be provided with a diet that is low in added sugars followed by a diet that is high in added sugars. Low Added Sugar Diet: Consumption of 10 days of a diet low in added sugars (5% of total caloric intake) |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Christopher Martens | University of Delaware | 302-831-7270 | cmartens@udel.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 8, 2024 | May 6, 2025 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 23, 2020 | May 6, 2025 | SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | May 12, 2023 | Apr 16, 2025 | ICF_002.pdf |
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A single-blind, randomized-crossover, controlled feeding study. Participants will be provided with 10-days each of a research diet containing low sugar (LS; 5% of energy from added sugars) vs. high sugar (HS; 25% of energy from added sugars) in a random order, separated by a 2-week washout.
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| High Added Sugar Diet | Other | Consumption of 10 days of a diet high in added sugars (25% of total caloric intake) |
|
| Day 10 of the diet |
| Revised Hopkins Verbal Learning Test (HVLT-R) Total Recall Memory | The Revised Hopkins Verbal Learning Test (HVLT-R) assesses verbal learning and memory, immediate recall and delayed recall from a list of 12 words. Immediate recall takes place over 3 trials (out of 12 correct responses each) Total recall is the sum of trials 1-3 (out of 36 correct responses). Delayed recall takes place 20-25 minutes after trial 3 and the participant must recall the entire list of words (out of 12 correct responses). | Day 10 of the diet |
| Revised Brief Visuospatial Memory Test (BVMT-R) Total Recall Score | The Revised Brief Visuospatial Memory Test (BVMT-R) assesses visuospatial memory and includes an immediate recall and delayed recall from images. Immediate recall takes place over 3 trials (out of 12 correct responses each) Total recall is the sum of trials 1-3 (out of 36 correct responses). Delayed recall takes place 20-25 minutes after trial 3 and the participant must recall or redraw all the images (out of 12 correct responses). | Day 10 of the diet |
| Seated Systolic Blood Pressure (mmHg) | Seated systolic blood pressure taken with arm at heart level after a 10-minute rest. Results are average of triplicate measurements | Day 10 of diet |
| Seated Diastolic Blood Pressure (mmHg) | Seated diastolic blood pressure taken with arm at heart level after a 10-minute rest. Results are average of triplicate measurements | Day 10 of diet |
| Day 10 of the diet |
| Pattern Comparison Processing Speed Test (Raw/Computed Score) | National Institute of Health (NIH) Toolbox Pattern Comparison Processing Speed Test Brief, computer-based assessment of processing speed in which participants quickly determine if two visual patterns are the same or different. For age 50-59, raw/computed score has a mean of 41.53 and standard deviation of 19.42 based on a normative dataset (Range = 11.00 - 65.00). For age 60-69, raw/computed score has a mean of 39.44 and standard deviation of 16.39 based on a normative dataset (Range = 7.00 - 64.00). A higher score indicates a better outcome. | Day 10 of the diet |
| Flanker Test (Raw/Computed Score) | Brief, standardized assessment of attention and inhibitory control, which are key components of executive function. For age 50-59, raw/computed score has a mean of 8.21 and standard deviation of 1.73 based on a normative dataset (Range = 3.88 - 9.74). For age 60-69, raw/computed score has a mean of 8.16 and standard deviation of 1.60 based on a normative dataset (Range = 3.63 - 9.59). A higher score indicates a better outcome. | Day 10 of the diet |
| Triglycerides (mg/dL) | Blood biomarkers triglycerides in mg/dL | Day 10 of the diet |
| Day 10 of the diet |
| Oxidative Stress | Blood biomarkers of oxidative stress (e.g. superoxide) using Electron Paramagnetic Resonance | Day 10 of the diet |
| BG001 |
| High Sugar, Low Sugar Diet |
Subjects will be provided with a diet that is high in added sugars followed by a diet that is low in added sugars.
|
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Seated systolic blood pressure (mmHg) | Seated systolic blood pressure taken with arm at heart level after a 10-minute rest. Results are average of triplicate measurements. | Mean | Standard Deviation | mmHg |
|
| Seat diastolic blood pressure (mmHg) | Seated diastolic blood pressure taken with arm at heart level after a 10-minute rest. Results are average of triplicate measurements. | Mean | Standard Deviation | mmHg |
|
| Height (cm) | Height measured (shoes off) on stadiometer. | Mean | Standard Deviation | cm |
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| Body mass (kg) | Body mass measured (shoes off) on scale. | Mean | Standard Deviation | kg |
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| Body mass index (BMI) | BMI calculated by using weight in kilograms (kg) divided by the square of height in meters (m2). | Mean | Standard Deviation | kg/m^2 |
|
|
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| Primary | Cerebrovascular Reactivity (Percent Increase in Cerebral Perfusion Normalized to the Increase in PETCO2 | Cerebrovascular reactivity (CVR) is the relative (percent) change in total cerebral perfusion measured using pseudo-continuous arterial spin labeling per mmHg change in end-tidal carbon dioxide (ETCO2) during a brief period of hypercapnia. Hypercapnia was induced by prospective end-tidal targeting (RespirAct, Thornhill Medical) in which a target change in end-tidal CO2 of +9 millimeters of mercury (mmHg) was set. Data were only analyzed if ETCO2 changed by at least 6.5 mmHg. All data were then normalized to the absolute change in ETCO2. | 5 participants did not have a CVR test with a ETCO2 changed by at least 6.5 mmHg. 2 participants did not perform the CVR test (due to discomfortable from the mask or not adequate space in the head coil). MRI was quenched (not working) for 2 participant during both diets. | Posted | Mean | Standard Deviation | percent increase in cerebral perfusion n | Day 10 of the diet |
|
|
|
| Primary | Hippocampal Stiffness (kPa) | Noninvasive brain imaging using Magnetic Resonance Elastography (MRE) to estimate tissue mechanical properties. Stiffness values are derived from the propagation of shear waves delivered to the head using vibration at 50 Hertz (Hz) from an acoustic driver system (Resoundant, Inc, Rochester MN) and reflects the distribution and organization of neurons, axons, and glial cells. A higher brain stiffness indicates greater tissue integrity. A nonlinear inversion algorithm estimated mechanical properties in the brain from acquired MRE displacement data to map shear modulus, G = G'+iG", where G' is the storage modulus and G'' is the loss modulus. From these parameters, stiffness is calculated, μ = 2*|G|^2 / (|G|+G') | MRI was quenched (not working) for 2 participant during both diets. The resoundant acoustic driver system did not work for 2 participants during the Low Sugar Diet. | Posted | Mean | Standard Deviation | kPa | Day 10 of the diet |
|
|
|
| Primary | Hippocampal Damping Ratio (Unitless Ratio) | Noninvasive brain imaging using Magnetic Resonance Elastography (MRE) to estimate tissue mechanical properties. Damping Ratio is derived from the propagation of shear waves delivered to the head using vibration at 50Hz from an acoustic driver system (Resoundant, Inc, Rochester MN) and reflects the relative elasticity of the brain tissue. A lower damping ratio indicates greater tissue integrity. A nonlinear inversion algorithm estimated mechanical properties in the brain from acquired MRE displacement data to map shear modulus, G = G'+iG", where G' is the storage modulus and G'' is the loss modulus. From these parameters, damping ratio is calculated, ξ = G"/2*G' | MRI was quenched (not working) for 2 participant during both diets. The resoundant acoustic driver system did not work for 2 participants during the LS diet. | Posted | Mean | Standard Deviation | unitless ratio | Day 10 of the diet |
|
|
|
| Primary | Revised Hopkins Verbal Learning Test (HVLT-R) Total Recall Memory | The Revised Hopkins Verbal Learning Test (HVLT-R) assesses verbal learning and memory, immediate recall and delayed recall from a list of 12 words. Immediate recall takes place over 3 trials (out of 12 correct responses each) Total recall is the sum of trials 1-3 (out of 36 correct responses). Delayed recall takes place 20-25 minutes after trial 3 and the participant must recall the entire list of words (out of 12 correct responses). | Posted | Mean | Standard Deviation | correct responses | Day 10 of the diet |
|
|
|
| Primary | Revised Brief Visuospatial Memory Test (BVMT-R) Total Recall Score | The Revised Brief Visuospatial Memory Test (BVMT-R) assesses visuospatial memory and includes an immediate recall and delayed recall from images. Immediate recall takes place over 3 trials (out of 12 correct responses each) Total recall is the sum of trials 1-3 (out of 36 correct responses). Delayed recall takes place 20-25 minutes after trial 3 and the participant must recall or redraw all the images (out of 12 correct responses). | Posted | Mean | Standard Deviation | correct responses | Day 10 of the diet |
|
|
|
| Primary | Seated Systolic Blood Pressure (mmHg) | Seated systolic blood pressure taken with arm at heart level after a 10-minute rest. Results are average of triplicate measurements | Posted | Mean | Standard Deviation | mmHg | Day 10 of diet |
|
|
|
| Primary | Seated Diastolic Blood Pressure (mmHg) | Seated diastolic blood pressure taken with arm at heart level after a 10-minute rest. Results are average of triplicate measurements | Posted | Mean | Standard Deviation | mmHg | Day 10 of diet |
|
|
|
| Secondary | Carotid-femoral Pulse Wave Velocity (CFPWV) (m/Seconds) | Carotid-femoral pulse wave velocity (CFPWV) assessed using applanation tonometry of the carotid artery and cuff-based assessment of the femoral pulse wave (SphygmoCor XCEL). CFPWV is calculated as the distance between the carotid and femoral pulse divided by the time-delay between pulses. A higher CFPWV is indicative of stiffer elastic arteries. | 1 participant did not have an accessible carotid artery via applanation tonometry for both diets | Posted | Mean | Standard Deviation | m/seconds | Day 10 of the diet |
|
|
|
| Secondary | Pattern Comparison Processing Speed Test (Raw/Computed Score) | National Institute of Health (NIH) Toolbox Pattern Comparison Processing Speed Test Brief, computer-based assessment of processing speed in which participants quickly determine if two visual patterns are the same or different. For age 50-59, raw/computed score has a mean of 41.53 and standard deviation of 19.42 based on a normative dataset (Range = 11.00 - 65.00). For age 60-69, raw/computed score has a mean of 39.44 and standard deviation of 16.39 based on a normative dataset (Range = 7.00 - 64.00). A higher score indicates a better outcome. | Posted | Mean | Standard Deviation | score on a scale | Day 10 of the diet |
|
|
|
| Secondary | Flanker Test (Raw/Computed Score) | Brief, standardized assessment of attention and inhibitory control, which are key components of executive function. For age 50-59, raw/computed score has a mean of 8.21 and standard deviation of 1.73 based on a normative dataset (Range = 3.88 - 9.74). For age 60-69, raw/computed score has a mean of 8.16 and standard deviation of 1.60 based on a normative dataset (Range = 3.63 - 9.59). A higher score indicates a better outcome. | Posted | Mean | Standard Deviation | score on a scale | Day 10 of the diet |
|
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| Secondary | Triglycerides (mg/dL) | Blood biomarkers triglycerides in mg/dL | 2 participants had missed blood draws on the High Sugar Diet. | Posted | Mean | Standard Deviation | mg/dL | Day 10 of the diet |
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| Other Pre-specified | Inflammatory Cytokines (%) | Biomarkers of inflammation (e.g. cytokines) from peripheral blood mononuclear cells | Not Posted | Day 10 of the diet | Participants |
| Other Pre-specified | Sleep Quality (%) | Sleep quality will be continuously measured for 10 days using an Actiwatch. | Not Posted | Day 10 of the diet | Participants |
| Other Pre-specified | Oxidative Stress | Blood biomarkers of oxidative stress (e.g. superoxide) using Electron Paramagnetic Resonance | Not Posted | Day 10 of the diet | Participants |
| 0 |
| 38 |
| 0 |
| 38 |
| 0 |
| 38 |
| EG001 | High Sugar Diet | Subjects will be provided with a diet that is high in added sugars followed by a diet that is low in added sugars. High Added Sugar Diet: Consumption of 10 days of a diet high in added sugars (25% of total caloric intake) | 0 | 38 | 0 | 38 | 0 | 38 |
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| Trial 3 Recall |
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| Total Recall |
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| Delayed Recall |
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| Trial 3 Recall |
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| Total Recall |
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| Delayed Recall |
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