bluuebunny/crossref_metadata_2025_split huggingface dataset:
378-P: Upregulation of Regenerating Gene IV and Hepatocyte Growth Factor in Cardiomyocytes by Intermittent Hypoxia and Its MicroRNA-Mediated Mechanism
Authors: TAKASAWA SHIN , ITAYA-HIRONAKA ASAKO , YAMAUCHI AKIYO , MAKINO MAI , SAKURAMOTO-TSUCHIDA SUMIYO , UCHIYAMA TOMOKO , TAKEDA YOSHINORI , KYOTANI YOJI , OTA HIROYO 
Published: June 2021

Sleep apnea syndrome is characterized by recurrent episodes of oxygen desaturation and reoxygenation (intermittent hypoxia [IH]) and is a risk factor for cardiovascular disease (CVD) and insulin resistance. However, the mechanisms linking IH stress and CVD remain elusive. We exposed rat H9c2 and mouse P19.CL6 cardiomyocytes either to sustained hypoxia (1% O2 [SH]), 70 cycles/24 h of IH (5 min SH/10 min normoxia [21% O2]), mimicking SAS patients, or normoxia for 24 h, analyzed mRNA expression and found that IH significantly increased the mRNA levels of regenerating gene (Reg) IV and hepatocyte growth factor (Hgf). Reg IV and Hgf in IH-treated cell medium were also increased. In order to analyze the IH-induced expression mechanisms of Reg IV and Hgf genes, we prepared reporter plasmids containing Reg IV and Hgf upstream of luciferase reporter gene, and transfected them into P19.CL6 cardiomyocytes. The promoter activities of the genes were not increased by IH. Target mRNA search of microRNA (miR)s revealed that both the mRNAs have a potential target sequence for miR-499. The miR-499 level of IH-treated cells was significantly decreased than that of normoxia-treated cells. To clarify the role of miR-499, miR-499 mimic and non-specific control RNA (miR-499 mimic NC) were introduced into P19.CL6 cells, and the IH-induced up-regulation of Reg IV and Hgf was abolished by introduction of miR-499 mimic. We also measured apoptosis of IH/SH-stimulated P19.CL6 cells by TUNEL method and found that SH but not IH increased apoptosis and that Reg IV and Hgf in cultured medium significantly reduced. The addition of Reg IV and/or Hgf in the culture medium attenuated the SH-induced apoptosis. These results indicate that IH stress increased levels of Reg IV and Hgf mRNA via the inhibition of the miR-499-mediated mRNA degradation, leading to protect cardiomyocytes against hypoxia -induced apoptosis.

Disclosure
S. Takasawa: None. A. Itaya-hironaka: None. A. Yamauchi: None. M. Makino: None. S. Sakuramoto-tsuchida: None. T. Uchiyama: None. Y. Takeda: None. Y. Kyotani: None. H. Ota: None.
379-P: Aldose Reductase Inhibition by AT-001 Prevents Diabetic Cardiomyopathy via Reducing Myocardial Fatty Acid Oxidation Rates
Authors: GOPAL KESHAV , KARWI QUTUBA G. , DAKHILI SEYED AMIRHOSSEIN TABATABAEI , WAGG CORY S. , PERFETTI RICCARDO , RAMASAMY RAVICHANDRAN , USSHER JOHN R. , LOPASCHUK GARY 
Published: June 2021

Cardiovascular diseases, including diabetic cardiomyopathy (DbCM), are major causes of death in people with type 2 diabetes (T2D). Several studies have suggested that aldose reductase (AR), an enzyme activated under hyperglycemic conditions, can alter cardiac energy metabolism and deteriorate cardiac function. We investigated whether inhibition of AR, using a next-generation inhibitor AT-001, can mitigate DbCM by modulating cardiac energy metabolism. Human AR overexpressing transgenic (hAR-Tg) and control C57BL/6J mice were subjected to experimental T2D (high-fat diet [60% kcal from lard] for 10-wks with a single intraperitoneal streptozotocin injection of 75 mg/kg at 4-wks). AR inhibition by AT-001 treatment (40 mg/kg/daily) for 3-wks significantly improved cardiac energetics in hAR-Tg mice with T2D. AT-001 treated mice exhibited significantly decreased cardiac fatty acid oxidation rates compared to the vehicle-treated mice (608 ± 66 vs. 1200 ± 176 nmol.min-1.g dry wt-1, respectively), which was accompanied by a decrease in cardiac oxygen consumption in AT-001 treated mice (44 ± 8 vs. 61 ± 11 µmol.min-1.g dry wt-1). Furthermore, treatment with AT-001 prevented cardiac structural and functional abnormalities present in DbCM, including diastolic dysfunction as reflected by an increase in the tissue Doppler E’/A’ ratio (1.6 ± 0.12 vs. 1.38 ± 0.1) and decrease in E/E’ ratio (26.6 ± 1 vs. 33 ± 4.9). AT-001 treatment also prevented cardiac hypertrophy as reflected by a decrease in LV mass (90.5 ± 2.2 vs. 125 ± 14 mg). We conclude that AT-001 prevents cardiac structural and functional abnormalities in DbCM, and normalizes cardiac energetics by shifting cardiac metabolism towards a nondiabetic metabolic state.

Disclosure
K. Gopal: None. Q. G. Karwi: None. S. Tabatabaei dakhili: None. C. S. Wagg: None. R. Perfetti: Stock/Shareholder; Self; Applied Therapeutics. R. Ramasamy: Consultant; Self; Applied Therapeutics, Research Support; Self; Applied Therapeutics. J. R. Ussher: None. G. Lopaschuk: None.
523-P: Psychosocial Impact of COVID-19 on Pediatric Diabetes
Authors: DIMENTSTEIN KAREN , YEE SHANIQUE , VALENZUELA JESSICA M. , PAN BERNARD , SNYDER MEG , WOLF RISA 
Published: June 2021

Background: Individuals with diabetes have been disproportionately affected by the COVID-19 pandemic. Data on the impact of COVID-19 on youth with T1D is scarce. We sought to determine the impact on youth with T1D and their families including the extent to which they experienced COVID-related disruptions and distress.
Methods: The COVID-19 Exposure and Family Impact Survey (CEFIS) was administered to caregivers of youth with T1D at two comprehensive diabetes clinics in the northeast and southern U.S. Items were scored and analyzed using SPSS. Themes were coded for open-ended questions. Health data were extracted from EMR.
Results: Mothers (85%) of 47 youth (72%NHW, 24%NHB, 4%H) with T1D (HbA1c M=8.3%) ranging from 6 to 17 years participated. Insulin pumps were used by 66% and CGMs by 17%. The most frequent COVID-related challenges endorsed were school/childcare closure (95.1%), education disruption (87.2%) and inability to visit/care for family (74.5%). Fewer caregivers reported difficulty accessing food (11.3%), necessary health care (9.4%), or medicine (5.7%). Areas of negative impact included child’s access to medical supplies (2.6), physical activity level and diet (M=2.7), as well as caregiver anxiety (M =3.2), mood (M =2.8), sleeping, eating, and exercise (M=2.7). Caregivers reported COVID-related distress for themselves (M=5.8) and their child (M=5.0; scale 1-10). Common themes regarding the impact of COVID-19 were increased health anxiety, limited social interaction, and routine disruption. Caregivers noted benefits in family cohesion. Both positive and negative impact on diabetes management were described by caregivers. Quotes from caregivers will be presented.
Conclusions: This ongoing study highlights early findings on the impact of COVID-19 on youth and families with T1D. Clinicians and researchers should consider the psychosocial impact of COVID-19 on youth with T1D and tailor diabetes care accordingly.

Disclosure
K. Dimentstein: None. S. Yee: None. J. M. Valenzuela: None. B. Pan: None. M. Snyder: None. R. Wolf: Consultant; Self; NEMA Research.
542-P: Club: A Novel Approach to Improve Self-Management in Youth with Type 2 Diabetes
Authors: CHANG NANCY T. , MUÑOZ CYNTHIA E. , YASUDA PATRICE M. , CHAO LILY 
Published: June 2021

Background: Adherence with treatment recommendations is challenging for many youths with type 2diabetes (T2D). Interventions to address their specific barriers are needed.
Objective: CLUB (Control your diabetes by Learning life skills and Understanding your Barriers) is a group intervention that targets the unique psychosocial needs of youth with T2D. The objectives are to foster peer support, enhance diabetes-related skill acquisition, and facilitate emotional adjustment to T2D and its management.
Methods: Youth with HbA1c &gt; 8% are referred to CLUB. CLUB includes four sessions over a 6-monthperiod. Youth meet as a group and parents convene separately. A pediatric psychologist facilitates the youth group. A bilingual nurse practitioner facilitates parent groups in English and Spanish. CLUB participants were matched with controls by gender, age, and duration of diagnosis.
Results: Of the 105 referred patients, 64 patients attended at least one session and 42 patients completed at least three sessions. Mean age of youth in the latter cohort was 15.3 years (SD 2.0yrs) and 70% were female. Ethnic background of the participants was predominantly Latinx. Median duration of diabetes diagnosis was 2.0 years (IQR 2.2 yrs). Mean HbA1cbaseline was 11.0%(SD 2.2%). Baseline HbA1c did not differ between cohorts. CLUB participation did not improveHbA1c (mean change in HbA1cControl =-0.14% and HbA1cCLUB=-0.32%, P=0.7283), but there was a positive correlation between HbA1c change (HbA1cfinal-HbA1cbaseline) and the time to completion of CLUB (P=0.0087).
Conclusion: CLUB is an innovative program that targets psychosocial barriers for youth with T2D. Though participants’ HbA1c did not improve, youth and their parents reported enjoyment of their experience. Preliminary data suggests that consistent participation in CLUB yielded a greater reduction in HbA1c compared to program completion over longer periods of time. This model and its potential to improve T2D health behaviors for diverse youth will be further examined.

Disclosure
N. T. Chang: None. C. E. Muñoz: None. P. M. Yasuda: None. L. Chao: None.
681-P: Effect of 3-Month Therapy with SGLT2 Inhibitors and GLP-1 Agonists on Ambulatory Blood Pressure in Patients with Type 2 Diabetes Mellitus
Authors: PAPAZAFIROPOULOU ATHANASIA , PAPANTONIOU STYLIANI S. , RALLATOU MARIA , MELIDONIS ANDREAS J. , ANTONOPOULOS STAVROS 
Published: June 2021

Background and Aims: It is known that SGLT-2 inhibitors and GLP-1 agonists show a favorable profile in the reduction of body weight as well as blood pressure (BP). Therefore, the purpose of this study is to evaluate the effect of SGLT-2 inhibitors and GLP-1 agonists on ambulatory BP in patients with poorly controlled type 2 diabetes (T2D).
Materials and Methods: A total of 74 patients with T2D: 42 on GLP-1 agonists (group Α) [20 men, mean age (±standard deviation) 60.6±9.4 years, HbA1c 8.5±1,1%, body mass index (BMI) 37.1±5.3 Kg/m2, T2D duration 10.1±4.3] and 32 on SGLT-2 inhibitors (group Β) [16 men, mean age 64.8±7.1 years, HbA1c 8.2±1.3%, BMI 32,1±9,2 Kg/m2]. All patients underwent a complete clinical and laboratory examination. Ambulatory BP recording at baseline and three months after initiation of treatment with the oscillometric Mobil-O-Graph NGW 24-hour ambulatory BP and PWA monitor (IEM; Stolberg, Germany).
Results: At baseline, mean daytime systolic and diastolic BP in group A were: 128.0±11.2 and 77.2±11.0 mmHg and in group B: 129.6±14.8 and 78.1±9.9 mmHg, respectively (P=0.78 and P=0.81, respectively, for the comparison between the study groups). Regarding the nighttime recordings of BP in group A, mean systolic and diastolic BP were: 127.5±12.6 and 73.7±14.2 mmHg. In group B, mean systolic and diastolic BP were: 126.3±12.5 and 74.1±8.7 mmHg (P=0.57 and P=0.67, respectively, for the comparison between the study groups). After 3-month therapy, mean systolic BP (group A versus B) was 124.0±7.8 versus 128.2±10.4 mmHg (P=0.04) and mean diastolic BP, 73.5±7.8 versus 78.3±7.8 mmHg (P=0.05). Regarding nighttime systolic BP was 118.6±11.1 (group Α) versus 117.4±9.3 mmHg (group Β) (P=0.54) and for mean diastolic BP 68.1±9.8 (group Α) versus 69.6±7.1 mmHg (group Β) (P=0.69).
Conclusion: Three-month therapy with GLP-1 agonists had a favorable effect of ambulatory systolic and diastolic BP compared to SGLT-2 inhibitors.

Disclosure
A. Papazafiropoulou: None. S. S. Papantoniou: None. M. Rallatou: None. A. J. Melidonis: None. S. Antonopoulos: None.
718-P: Long-Term Safety of Intranasal Insulin (INI) in Insulin-Dependent Type 2 Diabetes (T2DM-IDDM): A Safety Substudy of Memory Advancement by Intranasal Insulin in Type 2 Diabetes (MemAID) Trial
Authors: BECERRA LAURA APONTE , MENDEZ BRAHYAN GALINDO , KHAN FAIZAN , MANTZOROS CHRISTOS , NOVAK PETER , LIOUTAS VASILEIOS , NGO LONG H. , NOVAK VERA ,   MEMAID INVESTIGATORS, TREVINO J. 
Published: June 2021

INI has emerged as a potential treatment for T2DM-related functional decline and is safe in adults without T2DM. However, INI safety in T2DM-IDDM is unknown. We aimed to demonstrate safety of long-term INI use in T2DM-IDDM MemAID participants. We screened 86 participants with T2DM-IDDM, 14 were randomized (9 INI/5 Placebo), 9 started treatment (5 INI [60±14 years, 2 Female]; 4 Placebo [68±2 years, 1 Female]). Of those, 2-INI and 3-Placebo participants completed 24 weeks of treatment and 24 weeks of follow-up. Participants underwent one week of continuous glucose monitoring (CGM)(Medtronic IPro2) at baseline and after INI (Novolin® R ) or placebo initiation. HbA1c, fasting plasma and capillary glucose, and insulin were measured throughout the study. Insulin levels were unchanged across the study. In 2 INI-treated participants, HbA1c, fasting plasma and capillary glucose declined from baseline, but the average values were similar during treatment and follow up, and comparable to 3 placebo-treated participants. Both INI-treated participants had adjustments of IDDM regimens. Capillary glucose did not decline 2 hours after INI administration, and there were no interactions between INI and subcutaneous insulin. There were no INI-related serious adverse events. Of 13 hypoglycemia (HG) episodes across the study, 2 asymptomatic level-1 HG (15.4%) occurred in INI group and 7 (53.8%) in placebo group. There were 2 asymptomatic level-2 HG (15.4%) in both INI and placebo groups. INI therapy was not associated with serious adverse events or HG in older participants with T2DM-IDDM. This study may pave the way towards future larger studies evaluating the safety of concomitant administration of INI and subcutaneous insulin (NCT02415556).

Disclosure
L. Aponte becerra: None. B. Galindo mendez: None. F. Khan: None. C. Mantzoros: Advisory Panel; Self; Amgen Inc., GENFIT, Intercept Pharmaceuticals, Inc., Novo Nordisk, Regeneron Pharmaceuticals Inc. P. Novak: Other Relationship; Self; Dysimmune Foundation, Endonovo Therapeutics, Oxford Press. V. Lioutas: Consultant; Self; QMetis. L. H. Ngo: Consultant; Self; Five Islands Consulting, Other Relationship; Self; Radiological Society of America. Memaid investigators (j. trevino): n/a. V. Novak: Advisory Panel; Spouse/Partner; Endonovo Therapeutics, Inc., Consultant; Spouse/Partner; Dysimmune Foundtation, Other Relationship; Spouse/Partner; Oxford University Press.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK103902); U.S. Food and Drug Administration (IND107690); Novo Nordisk (ISS-001063), Medtronic (NERP15-0310); World Health Organization (UTN-U111-1175-1588)
Diabetes With Multiple Autoimmune and Inflammatory Conditions Linked to an Activating SKAP2 Mutation
Authors: Rutsch Niklas , Chamberlain Chester E. , Dixon Wesley , Spector Lauren , Letourneau-Freiberg Lisa R. , Lwin Wint W. , Philipson Louis H. , Zarbock Alexander , Saintus Karline , Wang Juehu , German Michael S. , Anderson Mark S. , Lowell Clifford A. 
Published: June 2021

OBJECTIVE
Multiple genome-wide association studies have identified a strong genetic linkage between the SKAP2 locus and type 1 diabetes (T1D), but how this leads to disease remains obscure. Here, we characterized the functional consequence of a novel SKAP2 coding mutation in a patient with T1D to gain further insight into how this impacts immune tolerance.

RESEARCH DESIGN AND METHODS
We identified a 24-year-old individual with T1D and other autoimmune and inflammatory conditions. The proband and first-degree relatives were recruited for whole-exome sequencing. Functional studies of the protein variant were performed using a cell line and primary myeloid immune cells collected from family members.

RESULTS
Sequencing identified a de novo SKAP2 variant (c.457G&gt;A, p.Gly153Arg) in the proband. Assays using monocyte-derived macrophages from the individual revealed enhanced activity of integrin pathways and a migratory phenotype in the absence of chemokine stimulation, consistent with SKAP2 p.Gly153Arg being constitutively active. The p.Gly153Arg variant, located in the well-conserved lipid-binding loop, induced similar phenotypes when expressed in a human macrophage cell line. SKAP2 p.Gly153Arg is a gain-of-function, pathogenic mutation that disrupts myeloid immune cell function, likely resulting in a break in immune tolerance and T1D.

CONCLUSIONS
SKAP2 plays a key role in myeloid cell activation and migration. This particular mutation in a patient with T1D and multiple autoimmune conditions implicates a role for activating SKAP2 variants in autoimmune T1D.
Dynamics of aerial and perennial biomass of two lucerne cultivars with different fall dormancy subject to two severities of cutting during the establishment phase
Authors: García Leonela Analía , Assuero Silvia Graciela , Blain Gabriel , Pereyra Matías Ezequiel , Berone Germán Darío 
Published: June 2021

The aim of this study was to quantify the impact of two cutting severities on the dynamics of aerial and perennial (root plus crown) biomass of lucerne (Medicago sativa L.) plants of two cultivars of contrasting fall dormancy rating during the establishment phase. We worked at Unidad Integrada Balcarce with two cultivars of lucerne (non-winter dormant: FD10; semi-winter dormant: FD6) and two cutting severities (40 and 100 mm) defining four treatments (FD6-40 mm, FD6-100 mm, FD10-40 mm and FD10-100 mm) under a completely randomized design. In both cultivars, increasing cutting severity produced a reduction in leaf area and number of nodes in the residual, resulting in a reduced production of aerial biomass during regrowth, given a reduction on shoot number. On the other hand, the effect of increased cutting severity on perennial biomass was only observed in plants of FD10 cultivar. This cultivar showed less perennial biomass when cut at 40 mm than at 100 mm, while no differences were observed between cutting heights in FD6 cultivar.
John Damascus’s Church-Singing Brotherhood in Nizhny Novgorod at Beginning of 20<sup>th</sup> Century
Authors: Arkhipova N. E. 
Published: June 2021

The organization, composition, financial condition and activities of the John Damascus’s singing brotherhood are considered. The relevance of the study is associated with the need to revive spiritual and moral values in modern Russian society. The novelty of the esearch lies in the fact that for the first time, according to the chronicle of the church press, the functioning of the brotherhood was reconstructed, the choir of which consisted of representatives of the city clergy, and the conductors were professional musicians. The author notes that, despite the increase in the number of performers in peacetime, the unstable composition of the choir did not allow them to achieve high performing skills. It is shown that the brotherhood performed organizational, missionary, spiritual, educational, charitable functions. It is proved that the work of the brotherhood contributed to the activation of concert and choral activities in the city, helped to preserve the ancient singing tradition, on the one hand, and introduced the audience to modern sacred music on the other hand. It is emphasized that in the conditions of the expansion of secularization at the beginning of the 20th century, charitable spiritual concerts organized by the brotherhood helped to maintain, strengthen and develop religious and moral feelings, thoughts, moods in listeners. It is concluded that the deteriorating living conditions during the war years, and then revolutionary events stopped the functioning of the organization.
Interpretation and Reconstruction of Traditional Rituals on Semiotic Approach (Shor Rite ‘Shachig’)
Authors: Kimeeva T. I. , Abramova P. V. , Nasonov A. A. 
Published: June 2021

The position is substantiated according to which the preservation of the rite as an object of ethnocultural heritage in modern conditions is possible through bringing it into a museum state. It is argued that this process should be based on the fixation of the rite during the period of its existence in the natural socio-cultural environment, the results of which were reflected in the field diaries of ethnographers stored in museum archives. The authors point to the main difference between the “inheri tor of tradition” and the “bearer of tradition”, which is the fragmentation and discreteness of the information available to the latter, which is insufficient to recreate the complex image of the traditional rite. The potential of the proposed methodology for interpreting and reconstructing traditional rituals is revealed on the example of the Shor rite ‘Shachig’. The authors analyze modern national-social variations in the interpretation of ethnographic information about the rite of the first third of the XX century. It is shown that the superficial processing of the information contained in the sources and the incorrect decoding of the codes leads to the transformation of the descriptions of all elements and the material component of the rite. As a scientifically grounded alternative, reconstruction and interpretation of this rite from the standpoint of a semiotic approach is proposed, based on a comprehensive analysis of all its elements (actional, verbal, objective) and considering temporal and local characteristics.
Literary, Methodological Paradigms: The Theme of Artsakh in the Works by Raffi and Muratsan
Authors: BALAYAN Zinaida 
Published: June 2021

In its internal divisions, literature is a science based on the complete principles of literary theory, philosophy, history, and analysis of the literary-artistic original (stylistics and contention), which in depth is unable to fully integrate the content of the subject.
That is why it is necessary to divide the components that are part of the subject, each of which in its turn forms an independent field of inquiry with its proposed method and methodology.
Effects of Ultraviolet-B Radiation in Plant Physiology
Authors: Nassour Rana , Ayash Abdulkarim 
Published: June 2021

Abstract
Over the past few decades, anthropogenic activities contributed to the depletion of the ozone layer, which increased the levels of solar ultraviolet-B (UV-B) radiation reaching the Earth`s surface. Generally, UV-B is harmful to all living organisms. It damages the cell`s Deoxyribonucleic acid (DNA), proteins, and lipids, and as a consequence, it affects the bio-membranes negatively. In this review, we summarize the major effects of UV-B in the plant`s main molecules and physiological reactions, in addition to the possible defence mechanisms against UV-B including accumulating UV-B absorbing pigments to alleviate the harmful impact of UV-B.
Stability Analysis of a Mathematical Model for the Use of Wolbachia to Stop the Spread of Zika Virus Disease
Authors: Anyanwu Michael C. , Mbah Godwin C. 
Published: June 2021

Summary
The use of wolbachia-infected mosquitoes to stop the spread of zika virus disease is modeled and analyzed. The model consists of a system of 10 ordinary differential equations which describes the dynamics of the disease in the human population, a wolbachia-free Aedes aegypti population, and a wolbachia-infected Aedes aegypti population used for disease control. A stability analysis of the disease-free equilibrium is conducted, which shows that it is both locally and globally asymptotically stable when the reproduction number is less than one. The result of the stability analysis shows that the spread of zika virus disease can be stopped, irrespective of the initial sizes of the infected human and mosquito populations, when wolbachia-infected Aedes aegypti are introduced in the area where the disease is endemic.