bluuebunny/crossref_metadata_2025_split huggingface dataset:
69-OR: Freestyle Libre System Use Is Associated with Reduction in Inpatient and Outpatient Emergency Acute Diabetes Events and All-Cause Hospitalizations in Patients with Type 2 Diabetes
Authors: BERGENSTAL RICHARD M. , KERR MATTHEW S.D. , ROBERTS GREGORY J. , SOUTO DIANA , NABUTOVSKY YELENA , HIRSCH IRL B. 
Published: June 2020

Continuous glucose monitors (CGMs) improve glycemic control compared with self-monitoring of blood glucose. We aim to describe clinical outcomes in people with type 2 diabetes (T2D) who received FreeStyle Libre® system.
IBM MarketScan™ Commercial Claims and Medicare Supplemental databases were used in this retrospective, observational analysis. MarketScan contains insurance billing claims for inpatient, outpatient, and pharmacy expenses. Cohort requirements included: de novo FreeStyle Libre system purchase in 2017 Q4-2018 Q2, diagnosis of T2D, ≥18 years old, fast- or short-acting insulin, and ≥6-months pre-CGM observation time. Primary outcome was acute diabetes events (ADE): hospitalization with hyper-/hypoglycemia as the primary diagnosis or outpatient emergency associated with a code of hyper-/hypoglycemia. Secondary outcome was all-cause hospitalizations. Andersen-Gill Cox regression compared event rates 6-months pre-/post-CGM.
The cohort (n=1,244, age 53.6±9.7 years, 53.8% male) experienced a reduction in ADE from 0.158 to 0.077 events/patient-year (HR: 0.49 [0.34 0.69]; P:&lt;0.001). Hospitalizations also reduced from 0.345 to 0.247 events/patient-year (HR: 0.72 [0.58 0.88]; P:0.002).
After FreeStyle Libre system purchase, T2D patients had lower rates of ADE and all-cause hospitalizations.

Disclosure
R.M. Bergenstal: Consultant; Self; Ascensia Diabetes Care, Johnson & Johnson. Other Relationship; Self; Abbott, Dexcom, Inc., Hygieia, Lilly Diabetes, Medtronic, Novo Nordisk A/S, Onduo, Roche Diabetes Care, Sanofi, UnitedHealth Group. M.S.D. Kerr: Employee; Self; Abbott. G.J. Roberts: Employee; Self; Abbott. D. Souto: Employee; Self; Abbott. Y. Nabutovsky: Employee; Self; Abbott. I.B. Hirsch: Consultant; Self; Abbott, Bigfoot Biomedical, Roche Diabetes Care. Research Support; Self; Medtronic, Omnipod.
690-P: Use of Physiological and Psychological States to Enhance Glucose Concentration Estimation
Authors: SEVIL MERT , HOBBS NICOLE , RASHID MUDASSIR , HAJIZADEH IMAN , ASKARI MOHAMMAD REZA , PARK MINSUN , QUINN LAURIE T. , CINAR ALI 
Published: June 2020

The accuracy of blood glucose concentration (BGC) estimation affects insulin dosing decisions. Wristband biosignals (Empatica E4) are used to estimate physical activity type and intensity, and psychological stress to enhance BGC prediction accuracy. Three cases are compared: (1) BGC prediction by using only continuous glucose monitor (CGM) data, which considers only meal effects and plasma insulin concentration (PIC); (2) Incorporating physical activity information to complement CGM data; and (3) Incorporating both physical activity and psychological stress information to complement CGM data. Twenty-eight experiments with seven subjects with T1D are conducted including various physical activities and acute psychological stress inducements. The subjects wore a CGM, insulin pump and E4 wristband during the experiments. Physical activities included treadmill running, stationary bicycling, resistance exercises and activities of daily living. Acute psychological stress inducements included the Trier Social Stress test, playing competitive videogames, solving arithmetic problems, and daily stressful events. The overall mean absolute errors (%) were 10.42, 8.69. and 8.42 for Cases 1, 2, and 3, respectively. The results illustrate that incorporating estimates of psychological and psychological effects improve the BGC prediction accuracy by 17.18% (Freidman’s ANOVA test, p-value &lt; 0.01).

Disclosure
M. Sevil: None. N. Hobbs: None. M. Rashid: None. I. Hajizadeh: None. M. Askari: None. M. Park: None. L.T. Quinn: None. A. Cinar: Research Support; Self; Dexcom, Inc., JDRF. Stock/Shareholder; Self; Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Novo Nordisk A/S, Tandem Diabetes Care.

Funding
National Institutes of Health (1DP3DK101075-01, 1DP3DK101077-01); JDRF (A18-0036-001)
692-P: Hyperglycemia Impairs Aerobic Adaptation to Exercise
Authors: MACDONALD TARA , PATHAK PRERANA , FERNANDEZ NATALIE M. , FREITAS ELLEN C. , HAFIDA SAMAR , MITRI JOANNA , LESSARD SARAH J. 
Published: June 2020

Improved aerobic exercise capacity (VO2max) has emerged as one of the most important health benefits of aerobic exercise training. However, hyperglycemia is associated with low VO2max in humans, even when physical activity levels are matched. To determine how glycemia influences aerobic adaptations with exercise training, we induced moderate hyperglycemia (+50-70 mg/dL vs. control) in mouse models that mimic the pathologies of type 1 or type 2 diabetes: 1) Low-dose Streptozotocin treatment (STZ), or 2) Western diet (WD) feeding. Normoglycemic mice acted as controls (CON). All mice completed ∼500 km of voluntary wheel running over an 8-wk aerobic training period, and achieved the expected metabolic benefits from exercise training. However, metabolic improvements were uncoupled from aerobic adaptation in hyperglycemic WD and STZ mice, who failed to improve VO2max beyond the level of sedentary controls. In contrast, CON mice had a 2-fold increase in VO2max in response to the same training intervention. In hyperglycemic models, blunted improvements in VO2max were associated with structural changes to muscle, including glucose-induced modifications to the extracellular matrix (e.g., glycation and collagen accretion), and reduced exercise-induced angiogenesis and oxidative fiber-type shifts. Thus, our data provide evidence that aerobic muscle remodeling, which is critical for augmenting VO2max, is impaired by hyperglycemia. In addition, we show that chronic hyperglycemia causes hyper-activation of a JNK/SMAD2 signaling network in muscle with acute aerobic exercise, which is a known molecular mechanism that inhibits aerobic adaptation. Accordingly, in human subjects, we show that impaired glucose tolerance strongly predicts hyper-activation of this inhibitory signaling network in conjunction with low VO2max. Taken together, we demonstrate that hyperglycemia, regardless of etiology, may interfere with fundamental adaptations to aerobic exercise training and negatively regulate improvements in VO2max.

Disclosure
T. MacDonald: None. P. Pathak: None. N.M. Fernandez: None. E.C. Freitas: None. S. Hafida: None. J. Mitri: Consultant; Spouse/Partner; Janssen Pharmaceuticals, Inc., kymera. Consultant; Self; national dairy council/local dairy council. Research Support; Spouse/Partner; AbbVie Inc., beigene, Janssen Pharmaceuticals, Inc. Research Support; Self; Kowa Pharmaceuticals America, Inc., national dairy council. Research Support; Spouse/Partner; pharma cyclic, TG therapeutics. S.J. Lessard: None.

Funding
American Heart Association (19POST34381036)
701-P: Effects of Exercise on Extracellular Matrix Modifiers in Subcutaneous Adipose Tissue of Obese Adults
Authors: VARSHNEY PALLAVI , RYAN BENJAMIN J. , AHN CHIWOON , SCHLEH MICHAEL W. , HOROWITZ JEFFREY F. 
Published: June 2020

Mechanisms underlying the direct effects of exercise on metabolic health (independently of weight loss) are poorly understood, and very little is known about the effects of exercise on adipose tissue. The purpose of this study was to examine the effects of exercise training on the key extracellular matrix (ECM) modifiers, matrix metalloproteinase 2 (MMP2) and MMP9, in abdominal subcutaneous adipose tissue (aSAT) of obese adults. Seven obese adults (BMI=33±4 kg/m2; age=32±6) completed 12 weeks of exercise training (either 45min of steady-state exercise at 70% HRmax or 10x1min intervals at 90% HRmax with 1min recovery between intervals), and they were required to maintain body weight throughout. aSAT biopsies were collected before training (Pre) and twice after training - 1 day post exercise (1d PEX) and again 4 days post exercise (4d PEX; to wash out the acute effects of exercise). Using standard immunoblotting methods, we found no evidence for effects of training on either MMP2 or MMP9. However, using gelatin zymography (a technique with more than 100-fold higher sensitivity than immunoblotting) we found a strong trend for an increased MMP9 abundance 1d PEX (3.7±1.0 vs. 3.0±1.4 arbitrary units (AU), for 1d PEX vs. Pre; P=0.08). Interestingly, however, MMP9 returned to Pre training levels by 4d PEX (1.9±1.3 AU; P&lt;0.05 vs. 1d PEX). Gelatin zymography can also allow for quantification of the active-form of MMPs, and we found trends for exercise training to increase MMP2 in both its active- (P=0.08 and P=0.22 for 1d PEX and 4d PEX vs. Pre, respectively) and inactive-form (P=0.13 and P=0.12 for 1d PEX and 4d PEX vs. Pre, respectively). We were unable to detect the active form of MMP9.
In summary, because increased abundance and activity of MMPs may alter the fibrotic content and composition of the ECM, exercise-induced increases in MMP2 and MMP9 within aSAT may contribute to favorable modifications within adipose tissue ECM of obese adults.

Disclosure
P. Varshney: None. B.J. Ryan: None. C. Ahn: None. M.W. Schleh: None. J.F. Horowitz: None.

Funding
National Institutes of Health (R01DK077966, P30DK089503, F32DK117522, UL1TR002240)
71-OR: Oligofructose Improves Small Intestinal Nutrient-Sensing Mechanisms via the Small Intestinal Microbiota
Authors: WENINGER SAVANNA N. , BEAUCHEMIN EVE , LANE ADELINA I.L. , MEYER RACHEL , DUCA FRANK 
Published: June 2020

Manipulations to the microbiota may serve as a potential treatment for obesity. Oligofructose (OFS), a nondigestible carbohydrate, beneficially alters the distal gut microbiome and results in decreased food intake and bodyweight, although the exact mechanisms remain unknown. Despite the importance of small intestinal (SI) gut-brain nutrient feedback mechanisms in regulating food intake and energy homeostasis, no studies have directly examined whether OFS can improve SI gut-brain signaling, potentially via changes in the SI microbiota. Given recent evidence highlighting the importance of SI microbiota on regulating metabolic homeostasis, we tested the hypothesis that OFS specifically improves SI lipid-sensing mechanisms controlling food intake, via manipulation of SI microbiota. Before any significant changes in body weight are observed, acute (3d) treatment with OFS in high fat (HF)-fed rats results in a significant suppression of 2hr food intake following an intralipid or liquid meal SI infusion (6kcal) compared to HF alone, likely due to a restored gut to brain signal. OFS treatment also increased jejunal CD36 gene and protein expression, which is known to mediate lipid-induced release of GLP-1. As such, OFS-treated rats exhibited significantly increased portal GLP-1 levels and c-fos, a marker neuronal activation, in the NTS of the hindbrain following intralipid SI infusion, compared to HF-fed rats. Importantly, transplant of SI microbiota from 3d OFS HF-fed donors into HF-fed rats recapitulated these results, demonstrating the importance of OFS-induced SI microbiota changes in restoring nutrient-induced gut brain signaling. These results highlight the importance of the small intestinal microbiota in energy regulation and identify a potential role of the small intestine and small intestinal nutrient sensing in the beneficial effects of OFS.

Disclosure
S.N. Weninger: None. E. Beauchemin: None. A.I.L. Lane: None. R. Meyer: None. F. Duca: None.

Funding
Arizona Biomedical Research Commission (NIA17-7401)
712-P: Safety and Efficacy of 36 Hours Prolonged Fasting on Glucose Metabolism in People with Type 1 Diabetes: A Crossover Trial
Authors: MOSER OTHMAR , TRIPOLT NORBERT J. , PFERSCHY PETER N. , OBERMAYER ANNA , KOJZAR HARALD , MADER JULIA K. , BRUNNER MARTINA , MUELLER ALEXANDER , YILDIRIM HAKAN , SOURIJ CAREN , ECKSTEIN MAX L. , SOURIJ HARALD 
Published: June 2020

Evidence is accumulating that prolonged fasting (PL) might evoke improvements in metabolic health. Since fasting is accompanied by numerous endogenous processes to equilibrate blood glucose concentration, its feasibility is disputable in people with type 1 diabetes (PWT1D). We aimed to assess the safety and efficacy of PL in c-peptide negative (^&lt; 0.9 ng/mL) PWT1D.
Methods: Glucose metabolism was assessed during the fasting period (CGM) and via a 75 g OGTT accompanied with the same bolus insulin dose after 12 (shortF) and 36 hours of fasting (longF). Area under the curve (AUC) was calculated following the trapezoidal rule. Safety was assessed by the number of hypoglycemic episodes (&lt; 70 mg/dL) during fasting. Data were analysed using a paired sample t-test or Mann-Whitney-U-test (p≤0.05).
Results: In total, 17 PWT1D (6 women, aged 37 ± 11 years, BMI 24.9 ± 2.9 kg/m2, 10 MDI) were included. 13 episodes of mild hypoglycemia occurred in 9 participants during the shortF versus 27 in 15 participants during the longF. Incidence of hypoglycemia per hour was similar in both arms (median [IQR] shortF: 0.08 [0 - 0.08] vs. longF: 0.06 [0.03 - 0.07], p=0.62).
Conclusion: PL did not increase the risk of hypoglycemia in PWT1D. Intriguingly, the AUC for glucagon was significantly higher after longF compared to shortF, potentially explaining the numerically lower number of hypoglycemic events during longF.

Disclosure
O. Moser: Other Relationship; Self; Dexcom, Inc., Novo Nordisk A/S, Sanofi. N.J. Tripolt: None. P.N. Pferschy: None. A. Obermayer: None. H. Kojzar: None. J.K. Mader: Advisory Panel; Self; Becton, Dickinson and Company, Eli Lilly and Company, Medtronic, Prediktor Medical, Sanofi-Aventis. Speaker’s Bureau; Self; Abbott, Eli Lilly and Company, Medtronic, Novo Nordisk A/S, Roche Diabetes Care, Sanofi-Aventis. M. Brunner: None. A. Mueller: None. H. Yildirim: None. C. Sourij: None. M.L. Eckstein: Research Support; Self; Dexcom, Inc., Novo Nordisk A/S, Sanofi-Aventis. H. Sourij: Advisory Panel; Self; Amgen, AstraZeneca, Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. Research Support; Self; Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. Speaker’s Bureau; Self; Boehringer Ingelheim International GmbH, Novo Nordisk A/S, Sanofi.
715-P: Diet Scores Associated with Increases in General and Abdominal Obesity in the Melbourne Collaborative Cohort
Authors: COURTEN BARBORA DE , KARIM MD NAZMUL , HODGE ALLISON 
Published: June 2020

The prevalence of obesity is increasing rapidly worldwide, increasing the risk of several common chronic diseases. To ascertain which of the three diet scores - Alternative Healthy Eating Index 2010 (AHEI), Dietary Inflammatory Index (DII) and Mediterranean Diet Score (MDS) was a better predictor of future obesity, assessed as body mass index (BMI) or waist to hip circumference ratio (WHR), in the Melbourne Collaborative Cohort Study (MCCS).Prospective cohort study in 27,834 men and women aged between 40 and 69 years at baseline (1990-94). Body size measures were taken at baseline and follow-up in 2003-7. Diet was measure at baseline using a 121-item food frequency questionnaire, along with confounders - age, sex, measure of socioeconomic status, smoking status, alcohol drinking status, physical activity level, country of birth, baseline body size measure (BMI or WHR as applicable). Regression coefficients and 95% confidence intervals for the association of dietary scores at baseline with BMI and WHR at follow-up 2 were generated separately using multivariate linear regression models adjusting for variables listed above and dietary energy intake. Both BMI and WHR at follow-up increased across quintiles of baseline DII (Q5 vs. Q1 BMI 0.4102 (0.2060, 0.6145); WHR 0.0094 (0.0061, 0.0128)), while for AHEI the association was inverse (Q5 vs. Q1 BMI -0.5139 (-0.6791, -0.3487); WHR -0.0107 (-0.0134, -0.0080). Only WHR at follow-up was inversely associated with categories of baseline MDS (G3 vs. G1 BMI -0.0540 (-0.2349, 0.1270); WHR -0.0040 (-0.0070, -0.0010)). Based on Akaike’s Information Criterion (AIC) and Bayesian Information Criterion (BIC) statistics, AHEI was a stronger predictor of increased body size at follow-up than the other diet scores. Poor quality/pro-inflammatory diets predicted future overall and abdominal obesity. The AHEI may provide the best way to operationalise this and capture subtle differences between the scores.

Disclosure
B. de Courten: None. M. Karim: None. A. Hodge: None.
722-P: Pictorial Carbohydrate Counting: Engaging Youth with Diabetes in Nutrition Education
Authors: THIVIERGE MEREDITH R. , WAHEED MYRA , SEEL MAUREEN , WOLF RISA 
Published: June 2020

Background: Carbohydrate counting is used to determine prandial insulin doses in pediatric diabetes management. Benefits to carbohydrate counting include improved glycemic control, improved diabetes-specific quality of life, and improved coping ability in daily life. Patients self-report knowledge and comfort in carbohydrate counting, but we have no quantifiable way to determine the accuracy of this self-report. Thus, we implemented nutrition quizzes with photos of popular foods to assess fundamental knowledge of carbohydrate counting.
Methods: Pictorial nutrition quizzes were developed to review basic, intermediate and advanced fundamentals of carbohydrate counting. The nutritionist administered the quizzes to children &gt;8 years of age, as part of regular outpatient diabetes follow-up visits. Children completed the quizzes independently and were allowed to use their insulin pump and phone to calculate insulin doses. Quiz responses and scores were recorded, in addition to visit hemoglobin A1c (HbA1c). Demographic and clinical data were extracted from the electronic medical record.
Results: Nutrition quizzes were completed by 103 youth (99 with T1D, 4 with T2). Mean age was 14.2 (SD 2.6), 44% female, 70% White, mean duration of diabetes 6 y (SD 4). 65% used insulin pumps, 68% used CGMs. All patients (n=103) completed 1 quiz, and 31 completed more than 1 quiz (range 2-5 quizzes). Patients with better glycemic control scored higher on nutrition quizzes. Mean A1c at initial quiz administration was 9%, and at follow-up was 8.6% (p=0.4).
Conclusion: Pictorial nutrition quizzes engage children and adolescents with diabetes in reviewing the fundamentals of carbohydrate counting and provide opportunity for nutrition intervention during routine diabetes clinical care.

Disclosure
M.R. Thivierge: None. M. Waheed: None. M. Seel: None. R. Wolf: None.
726-P: Mediterranean Diet Adherence and Association with Cardiometabolic Risk after Behavioral Weight Intervention in Older Adults
Authors: MILLER RACHEL G. , VENDITTI ELIZABETH M. , MARCUS MARSHA D. , GERMEROTH LISA J. , CONLON RACHEL P.K. , LEVINE MICHELE D. , COSTACOU TINA 
Published: June 2020

Adherence to a Mediterranean (Med) diet pattern, characterized by increased intake of fruits, nuts/seeds, vegetables, legumes, whole grains, seafood, yogurt and vegetables, and decreased intake of red/processed meats, refined grains, starches and added sugars, is associated with reduced cardiometabolic risk independent of total calorie intake or single nutrients. We examined whether adherence to Med diet was associated with risk factor change in the context of a behavioral weight management trial for U.S. community-dwelling older adults at elevated diabetes and cardiovascular risk. The Pitt Retiree Study (n=322) examined the impact of 12 weekly group lifestyle sessions on weight and cardiometabolic risk (BMI, waist, glucose, lipids, and blood pressure) in older adults (age 65-80 yrs). Dietary goals included calorie reduction, &lt;30% of total calories from fat, lean protein at most meals, and following USDA MyPlate guidelines but not a Med diet. Adherence to a Med diet pattern (0-14 score) was assessed at baseline, 4, 12, and 24 months and categorized as low (0-5), moderate (6-9), or high (≥10). The baseline median Med diet score was 6 (range 0-13), with 45% categorized as low, 50% moderate, 5% high. Women were more adherent than men (p&lt;0.01). Adjusting for sex, higher scores were correlated with older age (p=0.02), lower baseline BMI (p=0.01) and smaller waist (p=0.01). Median [IQR] scores improved at 4 months (+1 [0, +2] p&lt;.001) with 27% low, 63% moderate, 10% high. Each 1-unit Med diet increase was associated with -0.1 kg/m2 BMI (SE=0.04, p=.006) and -1.0 mmHg Systolic BP (SE=0.47, p=0.03) at 4 months. Med diet improvement was maintained at 12 (+1, [0, +2] p&lt;.001) and 24 months (n=299, +1 [0, +2] p&lt;.001). Adherence to a food pattern consistent with a Med diet improves after lifestyle intervention, even when not specifically prescribed, and is associated with weight and blood pressure benefits. Importantly, older adults sustain change in dietary quality over 2 years.

Disclosure
R.G. Miller: None. E.M. Venditti: None. M.D. Marcus: None. L.J. Germeroth: None. R.P.K. Conlon: None. M.D. Levine: None. T. Costacou: None.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (R18DK096404)
727-P: A Plant-Based Meal Affects Thalamus Perfusion Differently than a Conventional Meal: A Three-Group Randomized Crossover Study
Authors: KAHLEOVA HANA , KUDLACKOVA MICHAELA , TINTERA JAROSLAV , THIEME LENKA , VELEBA JIRI , MALINSKA HANA , OLIYARNYK OLENA , MARKOVA IRENA , HALUZIK MARTIN , PAVLOVICOVA RENATA , TURA ANDREA , PELIKANOVA TEREZIE 
Published: June 2020

Objective: We tested the effects of a plant-based meal on these brain regions.
Methods: A randomized crossover design was used to test the effects of two energy- and macronutrient-matched meals: a vegan (V-meal) and a conventional (M-meal) on brain activity, gastrointestinal hormones, and satiety in participants with type 2 diabetes (T2D; n=20), overweight/obese participants (O; n=20), and healthy controls (H; n=20). Brain perfusion was measured, using arterial spin labeling functional brain imaging; satiety was assessed using a visual analogue scale; and plasma concentrations of gut hormones were determined at 0 and 180 min. Repeated-measures ANOVA was used for statistical analysis. Bonferroni correction for multiple comparisons was applied. The Hedge’s g statistic was used to measure the effect size for means of paired difference between the times (180-0 min) and meal types (M-V meal) for each group.
Results:Thalamus perfusion was the highest in patients with T2Dand the lowest in overweight individuals (p=0.001). Thalamus perfusion decreased significantly after ingestion of the M-meal in men with T2D (p=0.04) and overweight men (p=0.004), and it decreased significantly after ingestion of the V-meal in healthy controls (p&lt;0.001). The effect size was -0.41 (95% CI, -1.14 to 0.31; p=0.26) for men with diabetes; -0.72 (95% CI, -1.48 to 0.01; p=0.05) for overweight/obese men; and 0.82 (95% CI, 0.09 to 1.59; p=0.03) for men with T2D. Changes in thalamus perfusion after ingestion of both test meals correlated with changes in satiety (r= +0.68; p&lt;0.01), fasting plasma insulin (r= +0.40; p&lt;0.01), C-peptide (r= +0.48; p&lt;0.01) and amylin (r= +0.55; p&lt;0.01), and insulin secretion at 5 mmol/l (r= +0.77; p&lt;0.05).
Conclusion: Thalamus perfusion decreased after the M-meal in men with T2D and overweight/obese men, and it decreased after the V-meal in healthy controls. The changes in thalamus perfusion were associated with changes in satiety and insulin secretion.

Disclosure
H. Kahleova: None. M. Kudlackova: None. J. Tintera: None. L. Thieme: None. J. Veleba: None. H. Malinska: None. O. Oliyarnyk: None. I. Markova: None. M. Haluzik: Advisory Panel; Self; Lilly Diabetes, Sanofi. Consultant; Self; Ethicon US, LLC. Speaker’s Bureau; Self; AstraZeneca, Mundipharma International, Novartis AG, Novo Nordisk A/S. R. Pavlovicova: None. A. Tura: None. T. Pelikanova: None.

Funding
Ministry of Health of the Czech Republic (AZV15-27338A, IN00023001)