bluuebunny/crossref_metadata_2025 huggingface dataset:
1809-PUB: Painful Diabetic Neuropathy—Patients Treated with High-Frequency (10 kHz) Spinal Cord Stimulation (SCS) Experience Significant Reductions in A1C and Weight
Authors: KLONOFF DAVID C. , LEVY BRIAN L. , JAASMA MICHAEL , BHARARA MANISH , NASR CHRISTIAN E. , CARAWAY DAVID L. , PETERSEN ERIKA , ARMSTRONG DAVID G.
Published: June 2023

Objective: Up to 9 million Americans have painful diabetic neuropathy (PDN), which can be debilitating. For PDN patients, 10 kHz SCS has been shown to provide mean pain relief of 77% at 24 months (24M), and here we report secondary, novel potential benefits for A1C and body weight.

Methods: Subjects received a 10 kHz SCS implant plus medical management for their pain and diabetes. Subjects were followed for 24M post-implantation. Key inclusion criteria were: PDN ≥12M refractory to medications, lower limb pain ≥5cm (10cm VAS), and A1C ≤10%. For T2D subjects, changes in weight were evaluated for all subjects and cohorts with pre-implant BMI ≥30 and ≥35, and changes in A1C were evaluated for cohorts with pre-implant A1C ≥7.0% and ≥8.0%.

Results: For cohorts evaluated, A1C and weight generally decreased with time (Fig. 1). For subjects with pre-implant A1C ≥8.0%, the mean A1C reduction was 0.52% at 6M (p=0.064) and 1.04% at 24M (p=0.007). For all subjects, the mean weight reduction was 1.8 kg at 12M (p=0.058) and 3.1 kg at 24M (p=0.003). For subjects with pre-implant BMI ≥35, the mean weight reduction was 5.4 kg at 24M (p=0.005).

Conclusions: Previously reported pain relief and sensory improvement, coupled with reductions in A1C and weight reported here, further demonstrate the benefits of 10 kHz SCS treatment in the comprehensive care of T2D patients with PDN.

Disclosure

D.C.Klonoff: Consultant; EOFlow Co., Ltd., Fractyl Health, Inc., Integrity, Lifecare, Inc., Rockley Photonics, Thirdwayv Inc. B.L.Levy: Advisory Panel; Nevro Corp., CeQur SA, Consultant; Nevro Corp., CeQur SA, Digma Medical. M.Jaasma: Consultant; Bone Health Technologies, Inc., Employee; Nevro Corp., Bone Health Technologies, Inc. M.Bharara: Employee; Nevro Corp. C.E.Nasr: Advisory Panel; Siemens, Horizon Therapeutics plc. D.L.Caraway: Employee; Nevro Corp. E.Petersen: Consultant; Abbott, Biotronik, Medtronic, Nalu, Nevro Corp., Presidio Medical, Saluda Medical, Vertos Medical Inc., Research Support; Nalu, Nevro Corp. D.G.Armstrong: Research Support; Medaxis LLC.

Funding

Nevro Corp.
1811-PUB: Real-World Safety of the Combined Use of Dapagliflozin and Metformin in Type 2 Diabetes Mellitus Patients in China—Post Hoc Analysis of the DONATE Study
Authors: GUO LIXIN , WANG JING , LI LI , YUAN LIN , CHEN SHENG , WANG HUI , LI TONGHUAN , QI LIN , YANG HONG
Published: June 2023

Background: Dapagliflozin is effective and well-tolerated in type 2 diabetes mellitus (T2DM) patients and is often combined with metformin in clinical practice, with or without other antidiabetic agents. Yet, real-world data on the safety of the combined use of dapagliflozin and metformin are limited.

Methods: The DONATE study assessed the safety of dapagliflozin in 2,990 Chinese T2DM patients who received ≥1 dose of dapagliflozin. This post-hoc analysis assessed the incidences of adverse events (AEs), serious AEs (SAEs), and AEs of special interest (AESIs) during the 24-week follow-up in patients receiving both dapagliflozin and metformin, with or without other antidiabetic agents.

Results: In total, 2,165 patients (72.4%) from the DONATE study received both dapagliflozin and metformin. Comparable with that observed in the overall population, of these patients, 780 (36.0%) had ≥1 AE: 197 (9.1%) were drug-related as judged by the investigator, 129 (6.0%) were serious, and 96 (4.4%) resulted in treatment discontinuation. Urinary tract infections (UTIs), genital tract infections (GTIs) and hypoglycaemia developed in 50 (2.3%), 32 (1.5%), and 23 (1.1%) patients, respectively. In patients receiving dapagliflozin and metformin without other antidiabetic agent (n=322), 86 (26.7%) had ≥1 AE: 12 (3.7%) were drug-related as judged by the investigator, 8 (2.5%) were serious, and 6 (1.9%) resulted in treatment discontinuation. UTIs, GTIs, and hypoglycaemia developed in 4 (1.2%), 2 (0.6%), and 1 (0.3%) patient, respectively. The incidences of AEs, SAEs, and AESIs were also low when dapagliflozin and metformin were used together with dipeptidyl peptidase-4 inhibitor (DPP-4i, 37.5%, 3.1%, and 6.9%) or insulin (36.5%, 7.1%, and 5.0%).

Conclusion: The combined use of dapagliflozin and metformin, with or without other antidiabetic agents such as DDP-4i or insulin, showed a good safety profile in Chinese T2DM patients in the real world.

Disclosure

L. Guo: None. J. Wang: None. L. Li: None. L. Yuan: None. S. Chen: None. H. Wang: None. T. Li: None. L. Qi: None. H. Yang: None.
1812-PUB: Safety and Effectiveness of Empagliflozin/Linagliptin FDC in Uncontrolled T2DM Patients with COVID-19 Infection
Authors: SENGUPTA ASOKTARU
Published: June 2023

Background: COVID-19 infection prognosis is known to worsen in patients with various co-morbidities particularly with uncontrolled diabetes mellitus and is often associated with increased serum levels of various inflammatory markers such as CRP, IL-6, D-dimer, LDH etc. Hence optimal glycemic care is crucial for a good prognosis in type 2 Diabetes (T2D) patients with COVID-19 infection. Efficacy and safety of Empagliflozin/linagliptin fixed dose combination (FDC) in T2D patients is well known. In the present study, the safety and effectiveness of Empagliflozin/Linagliptin FDC was evaluated in T2D patients diagnosed with COVID-19 infection.

Aim: To evaluate the safety, effectiveness of T2D patients with COVID-19 infection with empagliflozin/linagliptin FDC.

Methods: A single center, retrospective observational study included T2D patients who were on Empagliflozin/Linagliptin (25/5 mg) at the time of COVID-19 diagnosis and were followed up for 6 months. Laboratory (HbA1c, Ferritin, LDH, IL-6, CRP, D-Dimer) and clinical assessments (need for oxygen support & steroids) were done at baseline, 3rd, and 6th months. Repeated measures ANOVA was used to determine the mean difference at specified time intervals and any p-value < 0.05 was considered statistically significant.

Results: A total of 50 T2D patients were included with mean age (SD) was 57.44 ± 9.88 years. Patients treated with Empagliflozin/Linagliptin FDC at 6 months showed significant reduction in HbA1c (6.87 ± 0.22 mg/dL from 10.2± 0.9 mg/dL), CRP (8.9 ± 2.79 mg/dL from 99.2 ± 4.00 mg/dL), LDH (288 ± 45.12U/L from 675 ± 95.41U/L), ferritin (408.4 ± 131.00 ng/mL from 1100± 216.2 ng/mL), IL-6 (8.97 ± 2.40 pg/mL from 95.56 ± 23.4 pg/mL). Also, the need for oxygen support and daily steroid dose requirement had become lesser over 6 months.

Conclusion: Once daily Empagliflozin/Linagliptin (25/5 mg) FDC was found to be safe, effective, and well tolerated in non-critically ill T2D patients with COVID-19 infection.

Disclosure

A.Sengupta: None.
1819-PUB: Multicentric Real-World Evaluation of CGM Metrics across Urban and Semi-urban Dedicated Diabetes Care Centres in 887 T2DM
Authors: CHAWLA PURVI M. , PUNATAR DHARMEN H. , DESHMANE RAJESH , BHOJANE SONALI , CHAWLA MANOJ S.
Published: June 2023

We evaluated the CGM metrics using the Libre Pro across 7 centres in India enrolling 887 people with T2DM, from January - December 2022. CGM metrics were analysed for the Time in Range (TIR), Time Below Range (TBR), Time Above Range (TAR). The target range used for all CGM was as per ADA recommendation of 70-180 mg/dl. We excluded patients with complications of T2DM. The mean (±SD, 95% CI) estimated A1c, TIR, TBR, TAR % were 7 (±1.8, 6.9 to 7.1), 56 (±24, 54 to 58), 9.2 (±12, 8.3 to 10), 35 (±27, 33 to 36). There was a negative significant correlation between eA1c and TIR (Pearson r -0.69, 95% CI -0.72 to 0.65, p <0.0001). There was a negative significant correlation between eA1c and TBR (Pearson r -0.53, 95% CI -0.57 to 0.48, p <0.0001). There was a positive significant correlation between eA1c and TAR (Pearson r 0.86, 95% CI 0.85 to 0.88, p <0.0001). The findings is indicative of the mean TIR, as a reflection of the glycemic control, across several geographically spread centres with varied representation of urban and semi-urban settings, delivering diabetes care to a diverse patient population. The significant correlation of the CGM metrics is encouraging and TIR should be the prime focus to improvise the glycemic care, that would further help improve TBR and adopt CGM.

Disclosure

P.M.Chawla: None. D.H.Punatar: None. R.Deshmane: None. S.Bhojane: None. M.S.Chawla: None.
1821-PUB: Relationship between Time in Range and Glucose Management Indicator in Adolescents and Children with Type 1 Diabetes Mellitus
Authors: LEI MENGYUN , LV JING , MAI XIAODONG , DENG HONGRONG , WANG CHAOFAN , YANG DAIZHI , YANG XUBIN , XU WEN , YAN JINHUA
Published: June 2023

Objective: To investigate the relationship between time in range (TIR, 3.9-10.0mmol/L) and glucose management indicator (GMI) in adolescents and children with type 1 diabetes mellitus (T1DM) and explore the impact of coefficient of variation (CV) on their relationship.

Methods: Data derived from continuous glucose monitoring (CGM) and other clinical data (including age, duration of T1DM, and laboratory-measured HbA1c) were obtained from the annual follow-up of the Guangdong T1DM Translational Medicine Study. The patients under 18 years old were included. The patients were divided into CV≤36% group and CV>36% group by the attainment of CV. The relationship between TIR and GMI of both groups was assessed with correlation coefficient. Further, patients were divided into 4 groups by the interquartile range of CV. The linear regression model was used to calculate the TIR predicted value corresponding to the same GMI in 4 groups.

Results: The 56 eligible datasets collected from May 2014 to August 2021 were included. The median age, duration of T1DM, and laboratory-measured HbA1c were 14.00 (12.00, 16.00) years, 4.15 (1.66, 5.29) years, and 9.00 (7.65, 11.23) %, respectively. The median TIR, GMI, CV, and valid number of days the CGM device was worn were 60.73 (42.59, 77.72) %, 7.37 (6.78, 8.56) %, 30.38 (24.87, 34.94) %, and 3.39 (2.97, 4.84) days, respectively. TIR and GMI were highly linear correlated (R2=0.89, p<0.001), and a significantly higher Spearman’s correlation coefficient was observed in the CV≤36% group than in CV>36% group ((R2=0.92, p<0.001) vs. (R2=0.63, p=0.004)). When the GMI was 7%, the corresponding TIR predicted values gradually decreased with the increase of CV, which were 75.66% (CV≤24.87%), 73.48% (24.87%<cv≤30.38%), 69.16% (30.38%34.94%).

Conclusions: TIR and GMI were highly linear correlated in adolescents and children with T1DM. With constant GMI, the less the glycemic fluctuation, the higher the TIR.</cv≤30.38%), 69.16% (30.38%

Disclosure

M.Lei: None. J.Lv: None. X.Mai: None. H.Deng: None. C.Wang: None. D.Yang: None. X.Yang: None. W.Xu: None. J.Yan: None.

Funding

Science and Technology Planning Project of Guangzhou (202102010154)
1833-PUB: Effects of Lifestyle on Obesity and Hypertension in Adolescents—Data from Western India
Authors: HASNANI DHRUVI , JHA SANTOSH , SABOO BANSHI D. , HASNANI SHRIJI , JAMALPURE SNEHAL , CHAVDA VIPUL
Published: June 2023

Background and Objectives: Hypertension (HT) is a leading risk factor for blood vessel diseases worldwide and its prevalence is increasing among adolescents. Lifestyle changes cause increased obesity, thereby increasing the risk of developing HT. In this study, the prevalence of HT and associated risk factors were assessed in adolescents in Gujarat, India.

Methodology: Each of the urban and rural cohorts included 400 subjects, aged 14-18 years, with similar gender distributions. Physiological parameters, including body mass index (BMI) and blood pressure, were recorded, and a questionnaire was used to evaluate medical history and lifestyle patterns with an emphasis on food habits. The association between the recorded parameters and obesity and HT was evaluated.

Results: The prevalence of HT was higher in the urban cohort than in the rural cohort (20% vs. 17%), and a weak association with a family history of HT was observed in both cohorts. Obesity and high-fat diet had a moderate to relatively strong association with HT in both cohorts. More than 35% of the participants who regularly consumed junk food were hypertensive.

Conclusion: The changing lifestyle with less physical activity and increased consumption of high-fat and high-sugar diets may have been responsible for the increasing obesity among adolescents, thereby increasing the prevalence of HT. A systematic approach to the recognition, monitoring, prevention, and treatment of obesity is crucial for addressing this global health issue.

Disclosure

D.Hasnani: None. S.Jha: None. B.D.Saboo: None. S.Hasnani: None. S.Jamalpure: None. V.Chavda: None.
1842-PUB: Ischemic Stroke in Patients with Diabetes Mellitus during COVID-19 Pandemic in South Korea, Using National Emergency Department Information System
Authors: JEONG PARK MIN , YEON JANG SOO , MOOK CHOI KYUNG , HYUN BAIK SEI , JIN YOO HYE
Published: June 2023

Background: Coronavirus disease 2019 (COVID-19) put strain on patients using health care services, which results in suboptimal care for diseases requiring prompt management, such as ischemic stroke. Patients with diabetes mellitus (DM), high risk group of stroke, were compromised with routine diabetic care during pandemic. Until now, the influence of this outbreak on the management of ischemic stroke has not been clarified both in total and DM subjects.

Methods: This nationwide population-based study analyzed 11,734 patients diagnosed of acute ischemic stroke and underwent intravenous thrombolysis (IVT) or endovascular thrombectomy (EVT) during January 2019 (reference year) to December 2020 (pandemic year). The changes in the frequency of ED visit, treatment modality and outcomes by ischemic stroke were compared between pandemic and reference period. Subgroup analysis in DM patients was also performed.

Results: During COVID-19 pandemic, incidence of ischemic stroke available requiring for urgent procedures increased by 7.57% in South Korea (5,653 in 2019 vs 6,081 in 2020). In total subjects, time for symptom onset to ED visit and for ED visit to admission was significantly delayed. As a treatment modality, the rate of IVT increased, while that of patients applied mechanical ventilation decreased. Especially, DM patients aged more than seventies exhibited a significant higher chance to ICU admission rate during pandemic (p-value < 0.01). Nevertheless, there was no significant difference in hospital-stay days and in-hospital mortality both in total and DM subjects.

Conclusion: During COVID-19 pandemic, the incidence of ischemic stroke necessary for emergency care was increased and elderly DM patient showed a higher ICU admission rate. However, overall treatment outcome of ischemic stroke was preserved during this outbreak period in South Korea.

Disclosure

M.Park: None. S.Jang: None. K.Choi: None. S.Baik: None. H.Yoo: None.
1844-PUB: What Impacts Stress Coping Ability in Type 2 Diabetes When It Is Measured by Japanese Method—A Cross-Sectional Study
Authors: ONO YURIKO , SAKAI RYOSUKE , IWASE HIROYA , TANAKA TORU , FUKUI MICHIAKI
Published: June 2023

Stress can cause diabetes or elevated blood glucose levels. Previous researches showed that higher ability of stress coping leaded to better glycemic control. Sense of Coherence (SOC) is considered one of the abilities to cope with stress and promote health. The 3-item 7-point Japanese version of SOC (SOC-3), a shortened version of SOC-29 and SOC-13, was designed to be easier to use in clinical study. Since no studies have revealed factors associated with SOC scale as assessed by SOC-3 (SOC-3s), we examined factors associated with SOC-3s in persons with type 2 diabetes. We selected 1179 persons with type 2 diabetes who visited the diabetic outpatient clinic at our hospital from January 2018 to February 2020. Questionnaire is as follows. Regression analysis was performed to examine factors associated with SOC-3s. Responses were obtained from 785 persons (499 men and 286 women). In multivariate analysis, SOC-3s was significantly associated with HbA1c (β = -0.078, p = 0.035), duration of diabetes (β = -0.076, p = 0.045), exercise habits (β = 0.093, p = 0.014), drinking habits (β = 0.080, p = 0.035), regular meal times (β = 0.102, p = 0.007). Duration of diabetes and lifestyles were associated with SOC-3s in persons with type 2 diabetes besides glycemic management.

Disclosure

Y.Ono: None. R.Sakai: None. H.Iwase: None. T.Tanaka: None. M.Fukui: None.
1853-PUB: Extrapancreatic Effects of GIP on Bone
Authors: YAMAUCHI TAISUKE , NAKAMURA NOBUHISA , MIYABE MEGUMI , ITO MIZUHO , HOSHINO RINA , KANADA SAKI , SEKIYA TAKEO , MATSUBARA TATSUAKI , MIYAZAWA KEN , GOTO SHIGEMI , NARUSE KEIKO
Published: June 2023

Glucose-dependent insulinotropic polypeptide (GIP) exhibits extrapancreatic effects through the receptor for GIP (GIPR). In this study, we used Ni-Ti Closed Coil Spring (Ni-Ti) in GIPR-deficient mice (GIPRKO) and wild-type mice (WT) to investigate the effect of GIP on force-induced bone remodeling due to orthodontic tooth movement. It was investigated. Ni-Ti was attached between the maxillary bone and the maxillary left first molar (M1) of GIPRKO and WT, and mechanical load was applied by pulling the M1 in the mesial direction. Remaining amount and bone quality were measured. A histological examination of the maxilla was also performed. As a result, compared to WT, GIPRKO showed a significant increase in tooth movement distance and a significant decrease in residual alveolar bone mass. TRAP staining showed an increase in osteoclasts in GIPRKO compared to WT on the tooth moving side. We also found that GIPRKO reduced osteoblasts in the steady state and suppressed osteoblasts after tooth movement. These results suggest that GIPRK impairs bone remodeling through increased bone resorption due to mechanical load, and that GIP plays an important role in bone remodeling.

Disclosure

T.Yamauchi: None. S.Goto: None. K.Naruse: None. N.Nakamura: None. M.Miyabe: None. M.Ito: None. R.Hoshino: None. S.Kanada: None. T.Sekiya: None. T.Matsubara: None. K.Miyazawa: None.
1854-PUB: Benefits of Bariatric Surgery on Risk Cluster Assignment in Individuals at High Risk for Type 2 Diabetes
Authors: SANDFORTH LEONTINE , LEMBO ERMINIA , VERRASTRO ORNELLA , SANDFORTH ARVID , FRITSCHE ANDREAS , JUMPERTZ VON SCHWARTZENBERG REINER , MINGRONE GELTRUDE , BIRKENFELD ANDREAS L.
Published: June 2023

A recent data-driven classification of subjects at risk for type 2 diabetes (T2D) has identified three subtypes at high risk to develop T2D and/or complications. Among these, clusters 5 and 6 were specifically insulin resistant and both had a very high risk for nephropathy, despite the fact that cluster 6 had a delayed development of T2D. We hypothesized that particularly clusters 5 and 6 benefit from bariatric surgery (BS) in terms of risk reduction.

We investigated 72 obese individuals at risk for T2D who underwent BS and were followed up for up to 24 months (15.3±4.5 months). At baseline, 97% of subjects were assigned to high risk clusters 5 or 6. Cluster 5 had a mean BMI of 42.8±4.9 kg/m2 vs. 42.5±4.0 kg/m2 in cluster 6, p=0.3. At baseline, HOMA-IR was 8.3±4.9 in cluster 5 and 4.7±2.6 in cluster 6 (p<0.001). After BS, subjects from both clusters normalized HOMA-IR (1.7±1.0 vs. 1.5±1.0) with cluster 5 benefitting significantly more from BS (p group over time <0.001). Unadjusted HOMA-β did not differ between clusters before and after BS. Importantly, 93% of individuals switched to low risk clusters 2 and 4 after BS with comparable distribution of baseline cluster assignment (p=0.5, figure).

These data show that BS leads to a switch from high to low risk clusters in persons at risk for T2D and suggest that BS decreases the risk for future complications also in high risk individuals, especially in high risk cluster 5.

Disclosure

L.Sandforth: None. E.Lembo: None. O.Verrastro: None. A.Sandforth: None. A.Fritsche: Advisory Panel; Novo Nordisk, Lilly, Sanofi, Boehringer-Ingelheim, Speaker's Bureau; AstraZeneca, SYNLAB Holding Deutschland GmbH. R.Jumpertz von schwartzenberg: Other Relationship; Sanofi, Amgen Inc., Lilly, Novo Nordisk. G.Mingrone: Advisory Panel; Fractyl Health, Inc., Board Member; Novo Nordisk, Consultant; Novo Nordisk, Fractyl Health, Inc., ReCor Medical, Inc. A.L.Birkenfeld: None.
1855-PUB: Generation and Identification of Pik3r3 Gene Pancreatic Beta-Cell Knockout Mice Model
Authors: ZHU XIAO-RONG
Published: June 2023

Objective: To construct Pik3r3 gene pancreatic beta cell knockout mice by the Cre recombinase system, and provide a more specific animal model for the study of the role and mechanism of Pik3r3 in insulin secretion.

Methods: Pik3r3 flox/flox transgenic mice were constructed by CRISPR/Cas9 technology and hybridized with pancreatic beta cell specific Cre recombinase (Ins2-cre) tool mice. We identified their progeny genotype by PCR and sequencing technology. The knockout (KO) and their wild type (WT)mice were used to measure body weight, glucose tolerance, and insulin secretion level.

Results: pancreatic beta cell specific Pik3r3 gene conditional knockout mice, with the genotype of Pik3r3 flox/flox/CreT, were successfully constructed. Further studies showed that Pik3r3 KO mice had impaired glucose tolerance but no significant change in body weight compared with WT mice.

Conclusion: The Pik3r3 gene pancreatic beta cell knockout mouse model was successfully constructed, which provides a research platform for exploring the role of Pik3r3 gene in the development of diabetes.

Disclosure

X.Zhu: None.

Funding

National Natural Science Foundation of China (82000733)
26-LB: Identifying the Risk of Diabetic Retinopathy Progression Using Machine Learning on Ultrawide Field Retinal Images
Authors: NIGAM AMBER , SUN JIE , SUBHASH VARSHINI , SILVA PAOLO S.
Published: June 2023

Estimating the risk of diabetic retinopathy (DR) progression is one of the most important and difficult tasks when caring for individuals with diabetic eye disease. Current DR severity scales have informed clinicians on the progression risk and provided recommendations for follow-up and treatment. The use of artificial intelligence (AI) algorithms may improve in this process. In this study, we developed and validated machine learning (ML) models for DR progression from ultrawide field (UWF) retinal images, which were labeled for baseline DR severity and progression based on clinician review of the images and 3-year longitudinal follow-up using the Early Treatment Diabetic Retinopathy Study (ETDRS) severity scale. This dataset has 8 classes: no DR nonprogression (14.62%), Mild nonproliferative DR (NPDR) progression (10.16%) /nonprogression (10.73%), Moderate NPDR progression (10.1%) /nonprogression (15.85%), Severe NPDR progression (11.27%) /nonprogression (10.68%), and proliferative DR (16.55%). A total of 9970 unique images were split into the train, the validation, and the test datasets based on 60-20-20 proportions. The class imbalance was addressed during model building through data augmentation. The ResNet model fine-tuned on this dataset has a classification test accuracy of 81% and an AUC of 0.967 on the test dataset. The objective of the model is to reduce false negatives, which refers to predicting a class that is less progressive than the true label. The predicted labels for 91% of the images were either correct labels or were the labels with greater progression than the original labels. These findings demonstrate the accuracy and feasibility of using machine learning models for identifying DR progression developed using UWF images. Potentially, the use of machine learning algorithms may further refine the risk of disease progression and personalize screening intervals that may reduce costs and improve vision-related outcomes.

Disclosure

A. Nigam: None. J. Sun: None. V. Subhash: None. P. S. Silva: Research Support; Optos plc., Optomed, Speaker's Bureau; Novartis, Roche Pharmaceuticals, Bayer Inc.
51-OR: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Study of BI 456906 in People with Overweight/Obesity
Authors: LE ROUX CAREL , STEEN OREN , LUCAS KATHRYN J. , STARTSEVA ELENA , UNSELD ANNA , HENNIGE ANITA M.
Published: June 2023

Glucagon receptor (GCGR) agonism increases energy expenditure and glucagon-like peptide 1 receptor (GLP-1R) agonism reduces energy intake; thus, dual GCGR/GLP-1R agonists, such as BI 456906, may be more effective at treating obesity than mono GLP-1R agonists. This dose-finding study tested efficacy and safety of BI 456906 in participants (pts) with overweight/obesity.

This double-blind, placebo (PBO)-controlled study (NCT04667377) randomised adults with BMI ≥27 kg/m2 to weekly subcutaneous BI 456906 (0.6, 2.4, 3.6, 4.8 mg) or PBO for 46 weeks (thereof 20-week (W) rapid, bi-weekly dose escalation; 26-W maintenance). Primary endpoint was bodyweight (BW) change (%) from baseline (BL) at W46. Secondary endpoints included proportion of pts reaching ≥5, ≥10 or ≥15% BW loss from BL at W46.

In total, 387 pts were randomised (treated set [TS], N=386; full analysis set [FAS], N=384; n≈77 per arm). At BL (FAS) mean age was 49.1 years, BW 105.7 kg and BMI 37.1 kg/m2; 31.8% of pts were male. BI 456906 therapeutic benefit vs PBO was shown by a non-flat dose response curve of BW change (%) from BL at W46. Mean BW reduced with dose over 46 weeks (FAS; 0.6 mg, −6.2%; 2.4 mg, −12.5%; 3.6 mg, −13.2%; 4.8 mg, −14.9%; vs PBO, −2.8%). At W46, BW loss (FAS) of ≥5, ≥10 and ≥15% was reached by 82.8%, 68.8% and 54.7% of 4.8 mg BI 456906 pts and 25.9%, 11.1% and 5.6% of PBO pts, respectively. Pts reaching and staying on 4.8 mg BI 456906 achieved BW loss of 18.7% at W46. Adverse events (AEs) were reported by 90.9% of BI 456906 pts (TS; 0.6 mg, 90.9%; 2.4 mg, 89.7%; 3.6 mg, 92.2%; 4.8 mg, 90.9%) and 75.3% of PBO pts, mainly gastrointestinal (TS; 0.6 mg, 57.1%; 2.4 mg, 85.9%; 3.6 mg, 75.3%; 4.8 mg, 81.8%; PBO, 41.6%); 24.6% of BI 456906 pts and 3.9% of PBO pts stopped treatment, mainly during dose escalation. Serious AE incidence was similar in BI 456906 and PBO pts (TS; 0.6 mg, 1.3%; 2.4 mg, 2.6%; 3.6 mg, 7.8%; 4.8 mg, 5.2%; vs PBO, 6.5%).

Over 46 weeks, BI 456906 showed substantial BW loss efficacy with no unexpected safety concerns.

Disclosure

C.Le roux: Advisory Panel; Novo Nordisk, Boehringer Ingelheim Inc., Lilly, Herbalife International of America, Inc., Johnson & Johnson, Medtronic, GI Dynamics, Keyron Ltd. O.Steen: None. K.J.Lucas: None. E.Startseva: Employee; Boehringer Ingelheim International GmbH. A.Unseld: None. A.M.Hennige: Employee; Boehringer Ingelheim International GmbH.

Funding

Zealand Pharma A/S; Boehringer Ingelheim
Effect of incident laser wavelength on structural and morphological properties of Bi1.6Pb0.4Sr2Ca2Cu3Oy films grown by pulsed laser deposition
Authors: Romero-Sanchez M. , Juarez-Lopez J. M. , Nieto-Zepeda K. , Quiñones-Galvan J. G. , Santos-Cruz J. , de la L. Olvera M. , Contreras-Puente G. , de Moure-Flores F.
Published: June 2023

A Bi1.6Pb0.4Sr2Ca2Cu3Oy superconductor target was obtained by a solid-state reaction at 860 °C by 130 h. Afterward, Bi1.6Pb0.4Sr2Ca2Cu3Oy thin films were grown by pulsed laser deposition at room temperature, from pellets of the synthesized target, on (111) silicon substrates. Bi1.6Pb0.4Sr2Ca2Cu3Oy films were deposited using an Nd:YAG laser with two different incident wavelengths (532 and 1064 nm) and by varying the distance between the target and the substrate: 20, 25, and 30 mm. X-ray diffraction results showed that Bi1.6Pb0.4Sr2Ca2Cu3Oy films were obtained with Bi-2223 and Bi-2212 superconductor phases.
Security and inequality: evidence from Portugal
Authors: P. Carvalho Bruno , Esteves Mariana , Peralta Susana
Published: June 2023

This paper analyses human security in Portugal, and how it interact with inequality. We use representative survey data to discuss the individual determinants of several dimensions of human security that go beyond the narrow conception of the absence of physical threats, into a multidimensional perspective, encompassing environmental security, and living conditions. Albeit Portugal is one of the safest countries in the world, we document that women, low income groups, the elderly and younger people often feel less safe. We show, however, that in a broader perspective, Portugal fares less well, as income, food, housing and health security are, in many cases, higher in the country than in many other European Union countries
Optimal ordering policies in response to a disposable coupon
Authors: Zu A. , Yue M.
Published: June 2023

This study investigates a retailer's ordering strategy under the framework of the economic order quantity (EOQ) model. A supplier offers a retailer a disposable coupon and allows it to place a special order at any time in a promotion period. The promotion period is not necessary short and shortages are allowed throughout the time horizon. In addition to the special order time and the special order quantity, the retailer needs to decide whether to place some regular orders in the promotion period before placing the special order for the purpose of making better use of this coupon. We show that the coupon should be used to the retailer's first order in the promotion period regardless of the duration of the promotion period. Moreover, the retailer's maximum inventory level is higher than that in the classical EOQ model. We find that a longer promotion period can benefit the retailer by endowing it with more flexibility in its decision-making. Therefore, the supplier can improve the cash flow and reduce the overstock by integrating a disposable coupon with a longer promotion period. Numerous managerial insights are obtained from sensitivity analysis and numerical experiments.
Mathematical modelling of metrological traceability chains
Authors: Velychko Oleh , Gordiyenko Tetyana
Published: June 2023

Metrological traceability is a property of the measurement result and requires an established multi-level calibration hierarchy. The metrological traceability chain is established through the calibration hierarchy and is used to establish the metrological traceability of the measurement result. Approaches to the establishment of metrological traceability chains are based mainly on graphic images.

Special international guidelines and European recommendations on the measurement uncertainty are used to evaluate the measurement uncertainty during the calibration of measuring instruments. The measurement uncertainty necessarily increases along the calibration sequence and is different for different levels of the metrological traceability chain. The measurement uncertainty depends on measurement standards or measuring instruments used during calibration.

A mathematical model of the metrological traceability chain for different levels of the calibration hierarchy is proposed. This model includes, as components, such basic metrological characteristics for a certain level of the chain as the measurement range, measurement uncertainty, measuring instrument or measurement standard. As additional parameters for the metrological traceability chain, it is proposed to use data from the calibration certificate of the corresponding measuring instrument or measurement standard used at a certain level of the chain.

Recommendations regarding practical application of the developed mathematical model of the metrological traceability chain, which can be used for chains of any measurements, are proposed. They can be used to establish the required metrological characteristics for a certain level of the metrological traceability chain. Such a model and recommendations for its practical application can be used in national metrology institutes and calibration laboratories.
Implementation of NATO standards to improve the electromagnetic immunity and compatibility of equipment of the critical infrastructure objects
Authors: Neyezhmakov Pavel , Buriakovskyi Serhii , Vasylieva Olena , Velychko Volodymyr , Venislavskyi Fedir , Rudenko Serhii
Published: June 2023

Ensuring that domestic technical equipment meets modern safety and reliability requirements in accordance with NATO standards is a pressing problem in Ukraine. Without metrological support for testing the electromagnetic compatibility and immunity to powerful electromagnetic fields of natural and artificial origin, it is impossible to ensure reliable and safe use of modern electronic, electroenergetics and electric equipment in critical infrastructure facilities.

The paper presents the metrological traceability paths of the state measurement standards in the field of electromagnetic measurements, established at the NSC “Institute of Metrology”, to the SI units. The results of the research on the measurement standard of the electromagnetic field strength unit in the frequency range from 0.01 MHz to 43 GHz (NDETU EM-05-2021), established at the NSC “Institute of Metrology”, are described. The connection of the NDETU EM-05-2021 measurement standard with the measurement standards of the power unit of electromagnetic oscillations in coaxial and waveguide transmission lines and the standard of AC electric voltage is demonstrated.

The lists of tests in accordance with the AESTR-500 standard, which are supported by the measurement standards of the NSC “Institute of Metrology”, and the equipment that can be calibrated by the national measurement standards are given. The examples of tests for electromagnetic compatibility carried out in the testing centre of the State Enterprise “Kharkivstandartmetrologiya” are provided.

Based on the results of the developed statistical models at the Research and Design Institute “Molniya” for predicting the vulnerability to electromagnetic effects of atmospheric phenomena on critical infrastructure facilities, the examples of the distribution of lines of the equal potential (in kilovolts) on the ground surface in the short circuit mode and the distributions of probability density of lightning strikes are presented. The distributions of the equal potential lines on the ground surface in the short-circuit mode of high-voltage substations are modelled based on calculations.
Road lighting and mesopic vision
Authors: Nazarenko Leonid , Didenko Olena
Published: June 2023

Human beings perceive information from the environment by using their sense organs. Vision is believed to provide the most information. There are three categories of vision: scotopic, mesopic, and photopic vision. The activity of two types of light-sensitive receptors in the eye, cones and rods, is different for each category. Cones and rods have a unique ability to adapt to different levels of illumination. Adaptation is the ability of the human eye to adapt to changing lighting conditions. Thanks to this mechanism, the human visual system has the ability to operate in a very wide range of pupil illuminations, that is, at different adaptive levels. At very low adaptive levels, only the rods are active, and the vision is called scotopic. As adaptive levels increase, starting at 0.005 cd/m2, the rods become less active, meanwhile the cones become active, and then the vision is called mesopic. At adaptive levels above 5 cd/m2, only cones are active, and the vision becomes photopic. Cones and rods have different spectral sensitivities: rods are more sensitive to short wavelengths, while cones are most sensitive within the visible spectral range. Cones are concentrated mainly in the part of the retina of the eye that is used for direct (on-line) vision, while rods are localized only in the areas used for peripheral vision. As a result, in case of mesopic vision, the peripheral vision becomes better with light sources that have a relatively large component of short wavelengths. The same is true for the subjective perception of brightness. At low adaptation levels, more rods become active, and thus these benefits are greater at low illumination levels.

Since photometric units are based on photopic vision, these advantages are not obvious. Thus, the correction factors should be determined according to the spectrum of light sources, which is characterized by the S/P ratio, and the illumination levels of road lighting.

The International Commission on Illumination has prepared a standard (CIE 115:2010 Lighting of roads for motor and pedestrian traffic). The main goals of road lighting are to ensure visual performance, visual comfort and to keep drivers alert.
Monitoring of forest management. Prediction of area change
Authors: Mamonov Kostiantyn , Velychko Volodymyr , Pomortseva Olena , Gryanyk Volodymyr
Published: June 2023

The current problems of monitoring of the state and changes in areas of green plantings are considered. The assessment of dynamics of the distribution of forest park plantations would allow making decisions on taking appropriate measures for forest restoration or sanitary logging to maintain the areas of the “lungs of the city” at the appropriate level. The analysis of global trends in the use of GIS and remote sensing to study the situation with green plantings shows that this allows obtaining up-to-date and reliable information promptly. Namely, it enables quick monitoring of ecological aspects on large areas and significantly speeds up taking necessary measures, if necessary. The available approaches to observe the tasks of monitoring of green areas are analysed. The existing problems of assessing the state of the forest park economy in complex environments such as cities are proposed to be solved by using software products such as ERDAS IMAGINE and ArcGIS for processing and further analysis of satellite imagery of the area. To solve the task of predicting the change in the forest park economy area over time, modelling linear regression is proposed using the built-in programming language in the ArcGIS. The developed application with an intuitive interface will provide an opportunity to conveniently work with databases and attribute information, graphics and images. The development includes five options for performing calculations, which allows analysing the results in each of the anticipated scenarios. All calculations were performed on the example of the Kharkiv Forest Park “Sokolniki-Pomirki”. An algorithm for processing and analysing satellite images was developed. The proposed algorithm can be applied to increase the speed of monitoring of the state of forests and predicting changes not only in Kharkiv, but also in other cities in Ukraine and worldwide. The paper demonstrates the capabilities of GIS for monitoring of green areas, which allow performing similar work with minimal time costs. Thus, the GIS product is promising at the current stage of observing changes in the areas of green plantings.
Metrological studies of a reference installation for reproducing the mass flow of humid air
Authors: Serediuk Orest , Malisevych Vitalii , Tkachuk Vitalii
Published: June 2023

The relevance of the development and metrological studies of reference installations when working in a humid gas medium is considered. The concept of creating a reference installation for reproducing the mass flow of humid air is outlined. An algorithm for the operation of a reference installation has been developed, which provides for the generation of water vapour as a component of the gas flow. Based on the algorithm and operation features of a reference installation, a list of the considered type A uncertainties, which relate to the estimation of the air volume measured by a reference meter, duration of the control volume reproduction, mass of generated water vapour during the period of reproduction of the volume, and relative humidity of the ambient air, was formulated. Type B uncertainties are considered, which are determined by metrological characteristics of the used measuring equipment: reference gas meter, chronometer, hygrometer, manometer, thermometer, and instruments for measuring the mass of generated moisture. Algorithms for evaluating the standard uncertainty by using the standard reference data are given: pressure and density of saturated water vapours, and air density under standard conditions. The formula and algorithm for its metrological evaluation based on the uncertainty theory for determining the compressibility coefficient of the ambient air used during the operation of the installation, taking into account its relative humidity, are also presented. The expressions for evaluating the combined and extended uncertainties of the developed installation are given.

The developed model relates to the mass measurement of wet gas and allows assessing the influence of operating conditions of the installation on the indications of the mass flow measuring equipment of various operating principles, for example, thermo-anemometric, ultrasonic.

The developed metrological model can be used to estimate metrological characteristics of reference installations operating in different types of gaseous medium, including natural gas.
The evaluation of the measurement uncertainty of the thousand-seed weight in accredited testing laboratories
Authors: Samoilichenko Olha , Mokiichuk Valentyn
Published: June 2023

The evaluation of the measurement uncertainty of the seed quality indicators is an integral part of testing in accredited testing laboratories. The thousand-seed weight is one of the essential indicators, the limit values of which are not standardized, but are taken into account when determining the cost of a lot of seeds or seeding rates.

The developed method for evaluating the measurement uncertainty of the thousand-seed weight by measuring two weights of 500 seeds is presented in the paper. According to the analysis of a basic calculation formula, the impact of correctness and accuracy on the measurement uncertainty was assessed. It was shown that the major measurement uncertainty components are uncertainties of weighting and repeatability. The repeatability is advisable to be evaluated by Type В using the limit of repeatability, if the national standard specifies the testing method. The authors have analysed the conditions when other components can be neglected. The uncertainty budget and an example of its calculation were received.
Persepsi Orang Tua Terhadap Disiplin Belajar Anak Di Rumah Di Desa Lestari Indah
Authors: Sihombing Feni Biuty Febiola , Nainggolan Elizon
Published: June 2023

Tujuan Penelitian yang ingin dicapai yaitu untuk mengetahui persepsi orang tua terhadap disiplin belajar anak dirumah di Desa Lestari Indah kecamatan siantar kabupaten simalungun. Subjek penelitian ini adalah Orang Tua Siswa di Desa Lestari Indah. Penelitian ini merupakan penelitian deskriptif dengan pendekatan kuantitatif dan hanya menggunakan satu variabel. Penelitian ini menggunakan instrument berupa angket atau kuesioner. Teknik pengambilan sampel menggunakan rumus Slovin dan Proportional Sampling. Teknik analisis data dalam penelitian ini menggunakan teknik analisis deskriptif kuantitatif dengan menggunakan kategori dan persentase. Hasil penelitian diperoleh Persepsi Orang Tua Terhadap Disiplin Belajar Anak Di Rumah Di Desa Lestari Indah, Kecamatan Siantar, Kabupaten Simalungun, 10 Orang tua dalam kategori sangat baik (11%), 29 Orang tua dalam kategori baik (32%), 25 Orang tua dalam kategori cukup (28%), 26 Orang tua dalam kategori kurang (29%) dan 0% kategori sangat kurang. Kesimpulan dalam penelitian ini yaitu persepsi orang tua terhadap disiplin belajar anak di rumah di desa lestari indah kecamatan siantar kabupaten simalungun secara keseluruhan adalah baik. Saran dalam penelitian ini diberikan kepada orang tua dan peneliti lain
Implementasi Metode Karya Wisata Dalam Mengembangkan Aspek Kemampuan Sosial Emosional Anak Usia 4-5 Tahun
Authors: Soleh Ach Suryansyah Maulana , Musayyadah Musayyadah , Farida Siti
Published: June 2023

Penelitian ini bertujuan untuk menggambarkan bagaimana penerapan metode karya wisat dalam mengembangkan aspek kemampuan sosial emosional anak usia 4-5 tahun di Ra Asy-Syuhada’ Pamekasan. Penelitian ini menggunakan jenis deskriptif kualitatif. Subjek penelitiannya yaitu siswa kelompok A1 Ra Asy-Syuhada’ Pamekasan. Adapun teknik pengumpulan data yang digunakan dalam penelitian ini yaitu observasi, wawancara dan dokumentasi. Analisis data dilakukan melalui proses reduksi data, penyajian data dan penarikan kesimpulan. Hasil penelitian menunjukkan bahwa implementasi pendekatan saintifik dalam pembelajaran di Ra Asy-Syuhada’ Pamekasan mampu meningkatkan perkembangan sosial emosional anak. Hal ini dapat dilihat dari perubahan sikap pada anak yaitu anak lebih percaya diri, berani mengemukakan pendapatnya, menghargai orang lain, menjaga diri sendiri serta mampu bermain dengan teman sebaya. Adapun Faktor pendukung dalam kegiatan ini yaitu guru sebagai fasilitator, biaya karya wisata, kondisi peserta didik, media pembelajaran, dan lingkungan karya wisata. Serta penghambatnya yaitu waktu yang terbatas, tingkah laku anak yang berbedabeda sehingga terkadang peserta didik tidak dapat terfalsilitasi semua
Property rights to others' property in the context of updating the civil legislation of Ukraine
Authors: Kossak V.M. , Ilkiv O.V.
Published: June 2023

Ukraine has constitutionally established its European integration aspirations, and therefore ensuring effective and proper legal regulation of property rights to other people's property in the context of updating the civil legislation of Ukraine are important issues. Carrying out reforms in the context of European integration processes is intended to change and improve approaches to both the grounds for acquisition and termination of real property rights. Therefore, it is appropriate to identify trends in their development, taking into account proposals for their reform, since any significant change in this area will inevitably lead to a new quality of legal regulation of the studied relations. Regulation of property rights to other people's property should be carried out taking into account the impact on this sphere of legal relations of the "normative content" of the Association Agreement between Ukraine, on the one hand, and the European Union, the European Atomic Energy Community and their member states, on the other hand.

It has been expressed in the article a position on certain aspects of the legal regulation of the acquisition of ownership by acquisitive prescription, servitude, emphyteussis, superficies, acquisition or preservation of property without sufficient legal grounds. The issue of proper legal regulation of forced termination of rem rights to property has become especially relevant in modern conditions. Therefore, special attention has been paid to requisition as a basis for terminating real property rights.

The author concluded that the departure from the concept of the absoluteness of property rights was dictated by the change and expansion of the list of property rights, which in the modern period cannot be considered closed. The Civil Code of Ukraine emphasizes that other property rights to other people's property may be established by law. Interpreting this provision, one can come to the conclusion that the list of property rights defined in Art. 395 of the Civil Code of Ukraine is established by law, and not by agreement of the participants in property relations.