bluuebunny/crossref_metadata_2025 huggingface dataset:
Aadhaar Secure Travel Identity
Authors: Sonker Suhana
Published: May 2022

Abstract: This paper proposed a public transport system which emphasize on secure travel technique by using Aadhaar card as a travel card. In this study we seek to explain the use of mobile services like mobile ticketing in public transportation previously , this paper provides a brief glance at secure travel system, since the passengers flow in public transportation is increasing day by day as the population is increasing secure travel is an important social need of today which done by using Aadhaar card. Aadhaar card. Aadhaar consist of 12-digit unique number which is the unique identification authority of India (UIDAI).For each and every individual, transaction –ID for every customer will be unique. It presents a brief review on Aadhaar card, and discusses the scope and advantages oflinking Aadhaar card to fake travelers. Customerdetail will be stored in the database for each andevery route, thus it would be beneficial for retrieving the data from database in case any disaster or terrorist attack providing efficientand convenient mechanism for recharge facility for the customer make this system user friendly. Further we present various cases in which Aadhaar card may pose security threats. In this paper followed by a discussion on the loopholes in the existing system. We conducted literature survey based on the various research articles, leading newspapers, case studies and categorized the various cases into three categories. Aadhaar project is one of the significant projects in India to bring the universal trend of digital innovation. The launch of this project was focused on the inter- operability of various egovernance functionalities to ensure the better utilization ofInformation, Communication and Technology Infrastructure. Towards this Government of India has recently made Aadhaar card mandatory for many government applications, and also has promoted Aadhaar enabled transactions. There are many issues related to security and privacy of the Aadhaar data need to be addressed. This paper highlights such cases. Keywords: UID, Passport, RTO Adhaaar System.
Impact of mammals during foraging and trampling of vegetation in the taiga and forest-steppe natural and natural-anthropogenic complexes of the Pre-Urals and Urals
Authors: Dvornikov Mikhail G. , Saxonov Sergei V. , Bukina Lydia A.
Published: May 2022

Generalizations of territorial allocation of natural complexes (NC) on their identification in the taiga and forest-steppe protected and developed territories as the main stage of complex research providing structural and functional analysis of their condition when assessing the impact of mammals Alces alces L ., Capreolus pygargus pygargus Pallas, Cervus elaphus sibiricus Sever., Cervus nippon Tim., Sus scrofa L., Castor fiber L., Meles meles L., Meles leucurus Hodgsen, Ursus arctos L., when feeding on and trampling the plant component in specific biogeocenoses (BGC). At high biomass of herd domestic ungulates 150-180 kg/ha their interrelations on pastures are shown with limited amount of forage plants and impact on vegetation cover leads to negative changes. Biomass of wild animals (up to 10 kg/ha) does not exceed zonal structural parameters of BGC, their interrelations are shown locally, with a large number of plants and impacts of subpopulations are balanced in processes of forest formation, productivity, accumulation and destruction of plant mass, respectively, in substance-energy flows, providing a sustainable functioning of NC. In places of intensive activity of animals (in former NCs) there are synanthropic plant species that grow abundantly in other communities, where zooanthroponous foci of diseases dangerous to humans also arise, advancing to urbanized areas.
Rat hematological parameters of subacute multifrequency electromagnetic next-generation cellular communications exposure
Authors: Orlova Valentina S. , Perov Sergey Yu. , Lifanova Rano Z. , Pinegin Sergei A.
Published: May 2022

The cellular communication electromagnetic fields have become a significant physical environmental factor recently, which cannot but cause reasonable concern due to the possible adverse effects of human health. Experimental laboratory animal studies are an integral part of the development and substantiation maximal permissible levels, in which the blood system is an objective functional indicator of the electromagnetic field biological effects. Thus, the purpose of the research was to study the hematological parameters of the male and female rat blood of subacute multi-frequency electromagnetic exposure from cellular communication systems and possible long-term biological effects. The object of research was male and female Wistar line rats. There were multi-frequency 30-days electromagnetic field exposure with 500 μW/cm2 power density at 3.5, 28 and 37 GHz summary. Hematological parameters of peripheral rat blood of the experimental and control groups were determined at the end of 30 days of exposure and 30 days after exposure. 30 days exposure did not lead to statistically significant changes in the blood cell composition in either male or female rats compared with sham exposure. In post exposure period (30 days after), significant changes in hematological parameters shown female rats only, which consisted in a decrease in the average content (MCH) and the average concentration (MCHC) of hemoglobin (Hb) in erythrocyte (RBC), the level of leukocytes (WBC), lymphocytes (LYM) and an increase in monocytes (MON). There were no statistical changes in all hematological parameters in male rats. The research results suggest the development of aftereffect adaptive reactions in rats upon completion of subacute electromagnetic exposure and their correlation to the effect depending on the sex of the animal.
Phytosozological study of natural monuments to determine the ecological status of specially protected natural areas
Authors: Volodkin Alexey A. , Larionov Maxim V.
Published: May 2022

The article gives a phytosozological assessment of natural monuments of regional importance in the Penza region, based on a number of phytosozological criteria that characterize the vegetation cover and their ecological state. The assessment is based on such criteria as the degree of study of the vegetation cover of the territory, the demonstration (reference) value, the area occupied, the anthropotolerance of the vegetation cover, the coenotic diversity of the territory, the total number of species diversity of vascular plants, the number of species listed in the Federal and regional Red Books, the degree transformation and recovery potential. The assessment used is of interest as a test express system that allows you to quickly assess the dynamics of the main qualitative and quantitative indicators of natural complexes. On the territory of the Penza region, located mostly on the western slope of the Volga Upland, and geobotanically located within the forest-steppe zone, in order to preserve biological and landscape diversity, 90 natural monuments of regional significance were identified on an area of 627.4 km2, which is 1.44% from the territory of the region. The highest concentration of natural monuments is noted in the north-east of the region, the most elevated and wooded part of the region. The largest area of more than 40 thousand hectares was noted in the Vyshe-Moksha botanical-geographical region. The largest number of monuments, of which 70% are botanical, are noted in the Prisursky botanical-geographical region with an average rating score of 62.2. The maximum score was noted at the natural monument Ardymsky Shikhan. The largest number of hydrological monuments of nature are located in the Zasursky and Prisursky botanical and geographical regions, which is associated with the location of the Sura River basin in these regions. The largest number of zoological monuments is located on the territory of the Vyshe-Moksha botanical-geographical region. The results obtained are necessary to determine the dynamics and directions of the processes of conservation and restoration of the composition of the flora and fauna of unique communities of regional natural monuments, as well as to increase the level of representativeness and ecological status, which in the future will allow monitoring changes in ecosystems.
First results of assessment of transport pressure on the RUDN University campus and the South-West Forest Park
Authors: Redina Margarita M. , Khaustov Aleksandr P.
Published: May 2022

Preliminary results of the evaluation of transport pollution of the RUDN University campus (Moscow) and adjacent forest park are presented. These objects are under the conditions of intensive road and highway impact. The assessment of the load is carried out on the basis of data from the environmental monitoring system in operation since 2017, information from the accounting of vehicles on highways, using specific emission indicators (established experience). The territory is considered as a representative experimental ground for studying and modeling the flows of various types and forms of pollutants in the “atmosphere - soil - plants” system, as well as greenhouse gas flows. Such a variety and density of materials make it possible to reliably identify areas of influence of traffic flows on the territory and simulate the migration of pollutants. The focus is on tire wear products, asphalt, as well as engine emissions: solid particles and polycyclic aromatic hydrocarbons. The results obtained indicate a significant level of load and generally correspond to modern estimates of total transport loads in Moscow.
The determination of cut-off points of the visceral adiposity index in predicting metabolic syndrome, insulin resistance, diabetes mellitus, and hypertension
Authors: KILIÇ TÜRK Hatice , PEKGÖR Selma , ERYILMAZ Mehmet
Published: May 2022

Introduction: The visceral adiposity index is a reliable indicator of visceral adipose tissue dysfunction. The aim of this research was to determine the cut-off points of the visceral adiposity index in predicting metabolic syndrome, insulin resistance, type 2 diabetes mellitus, and hypertension at specific age ranges and in both sexes separately.Methods: This research is both descriptive and analytical. The research was conducted with 951 participants aged 18 and over between July 2019 and July 2020. 51 participants that did not meet study criteria were excluded from the research. The research was completed with a total of 900 participants, 577 females and 373 males. A physical examination and anthropometric measurements (height, weight, waist circumference, and blood pressure) of all participants were conducted. After 12 hours of fasting, the HDL, TG, glucose, and insulin levels of participants were measured. The blood pressure of participants was measured after 15 minutes of rest. Adult treatment panel 3 criteria were used for the diagnosis of metabolic syndrome. A homeostatic model assessment was calculated. The visceral adiposity index is calculated in the entire population for the prediction of metabolic syndrome, insulin resistance, diabetes, and hypertension: women, men, age groups 18–30, 31–40, 41–50, 51–65, 66 and over.Results: Cut-off points of the visceral adiposity index in predicting metabolic syndrome were 4.53 in the total population and males, 4.28 in females, 4.76 in the 18-30 age range, 4.96 in the 31-40 age range, 4.87 in the 41-50 age range, 5.04 in the 51-65 age range, and 4.59 in the age range 66 and above. Cut-off points of the visceral adiposity index in predicting insulin resistance were 4.24 in the total population and females, 4.68 in males, 3.45 in the 18-30 age range, 4.15 in the 31-40 age range, 4.66 in the 41-50 age range, and 4.87 in the 51-65 age range. Cut-off points of the visceral adiposity index in predicting type 2 diabetes mellitus were 4.89 in the total population, 6.43 in females, 7.02 in the 31-40 age range, 7.29 in the 41-50 age range, and 5.98 in the 51-65 age range. Cut-off points of the visceral adiposity index in predicting hypertension were 4.26 in the total population, 4.07 in females, 4.64 in the 18–30 age range, and 4.43 in the 51–65 age range.Conclusions: The visceral adiposity index can be used to predict metabolic syndrome, insulin resistance, type 2 diabetes mellitus and hypertension.
The effect of depression and related psychosocial factors on disease activity in rheumatoid arthritis
Authors: TEKİN Murat , OĞUZ Aytekin
Published: May 2022

Introduction: Rheumatoid arthritis is one of the most common inflammatory chronic diseases worldwide. Depression is common in patients with rheumatoid arthritis. The relationship between depression and rheumatoid arthritis is a matter of curiosity, and it is thought that there is a bidirectional interaction between them. Depression is an important health problem that requires treatment. Therefore, it is essential to determine the conditions that call for more attention in terms of depression when following rheumatoid arthritis patients in primary care.Methods: Patients who applied to the rheumatology outpatient clinic, followed up for at least 1 year, and were diagnosed with rheumatoid arthritis according to the American College of Rheumatology (ACR) criteria were consecutively invited to the study. A total of 110 people, 18 men and 92 women, accepted the invitation. Beck Depression Inventory (BDI), Health Assessment Questionnaire (HAQ), and visual analogue scale (VAS) were filled together with the questionnaire developed by the researcher. In the joint examination of the patients, the number of tender joints and swollen joints were noted. Disease Activity Score (DAS28) was calculated and noted by measuring C Reactive Protein and erythrocyte sedimentation rates (ESR) in earlier tests performed on the patients. Rheumatoid factor status was recorded at the time of diagnosis or by checking the follow-up records.Results: In rheumatoid arthritis (RA) patients, the BDI score was higher in people with other chronic diseases and those who felt the need to apply to a psychiatry clinic. The BDI score was higher in patients with other chronic diseases and those who felt the need to apply to a psychiatry clinic for rheumatoid arthritis. RA patients with high BDI scores also had high DAS28 and HAQ scores. In addition, disease activity was significantly correlated with RF positivity.Conclusion: Rheumatoid arthritis patients should be evaluated for depression. Depression evaluation should be done more carefully in cases with high disease activity, other chronic diseases, and those who feel the need to apply to a psychiatry clinic.
Criterios teóricos que sustentan la formación docente continua en Educación Parvularia chilena en y para la diversidad
Authors: Mujica-Stach Ana Milena , Casas-Ernst Jacqueline A. , Peña-Rojas Cecilia C.
Published: May 2022

La educación en Chile reclama una mirada hacia la diversidad, entendiéndola a través de las categorías, variedad y distinción. Es así como desde la formación continua emerge la necesidad de formular criterios teóricos en educación parvularia en y para la diversidad. La metódica asumió un enfoque cualitativo bajo el tipo interpretativa-participativa de campo, con apoyo de la Teoría Fundamentada y su Método Comparativo Continuo. Las técnicas empleadas fueron entrevistas en profundidad y la observación participante. Los informantes claves fueron cinco educadoras con más de cinco años de experiencia laborando en Educación Inicial de la Región de Los Lagos, Chile. Los hallazgos se obtuvieron de la interpretación de las situaciones empíricas, de este modo se esclarecieron dialécticas y actuaciones de las educadoras, con información sobre conocimientos y experiencias orientadoras hacia la diversidad. Se concluye que los criterios teóricos permitirán de manera acertada la formación del docente para desarrollar competencias para lograr la atención de la diversidad.
Repositioning an old antihelminthic agent of niclosamide in human disease and cancer
Authors: Wang Guiling , Du Jinxiu , Wang Zhan , Ren Junyi , Wang Huan , Liu Jia
Published: May 2022

Niclosamide is a FDA-approved anthelminthic drug for the treatment of
parasitic infection. However, over the past few years, the increasing
evidence has shown that Niclosamide could treat diseases beyond
parasitic diseases, which include metabolic diseases, immune system
diseases, bacterial and viral infections, other types of diseases and
cancer. Therefore, we systematically review the pharmaceutical
activities and therapeutic prospects of Niclosamide in human disease and
cancer, and summarize the related molecular mechanisms and signaling
pathways, which provides theoretical support for the new therapeutic
value of old drug.
A case of atrial septal defect closure relieving refractory migraine
Authors: Hoshina Yuta , Iijima Hiroyuki , Kubota Mitsuru , Murakami Tsutomu , Nagai Akira
Published: May 2022

The effectiveness of patent foramen ovale closure for migraine has been
previously discussed. By contrast, very few studies have reported the
association between migraine and atrial septal defect closure. Here we
report a case in which atrial septal defect closure effectively relieved
migraine headaches.
Analysis of spatial-temporal variations and driving factors of typical tail-reach wetlands in the Ili-Balkhash Basin, Central Asia
Authors: Cao Yijie , Ma Yonggang , Liu Tie , Li Junli , Zhong Ruisen , Wang Zheng , Zan Chanjuan
Published: May 2022

In this study, wetlands in the Ili River Delta (IRD) from 1975 to 2020
were extracted based on Landsat images using the object-oriented method;
changes in the wetland area, wetland landscape pattern, NDVI and NPP
were analyzed; and the contributions of natural and human factors to
wetland evolution were quantified. The results indicated that (1) From
1975 to 2020, the wetland area of the IRD showed an increasing trend,
and changes in the wetland area were mainly found in the middle part of
the delta near the Saryesik Peninsula. (2) The wetland landscape pattern
in the IRD changed markedly from 1975 to 2020. The dominant patches of
the wetland in the middle of the delta continued to expand; the patch
aggregation index (AI) increased, and the patch fragmentation index
(LFI) decreased. (3) From 2000 to 2020, the average annual normalized
difference vegetation index (NDVI) and net primary productivity (NPP) in
the IRD increased, which is consistent with the change in wetland
expansion. (4) Inflow to the delta from the Ili River and the water
level of Balkhash Lake are significantly correlated with the wetland
area, which are the dominant factors driving wetland evolution; and
water evaporation from the Kapchagay Reservoir and irrigation water
diversion on the left bank of the reservoir obviously intensified the
process of lake water level decline and wetland degradation during 1970
to 1985. These results can provide scientific background for making
informed ecological protection decisions in the Ili River Delta under
the impacts of climate change and human activities.
Assemblages of Myxomycetes associated with Cocos nucifera L. trees
Authors: Sá Camila Estelita Vogeley Alves de , Ferraz Luiz Gonzaga Biones , Cavalcanti Laise De Holanda
Published: May 2022

Arecaceae plants provide favorable microhabitats for the development of myxomycetes, but researches focusing on myxomycetes associated with palm trees are scarce. The myxobiota present on Cocos nucifera L. was evaluated in coconut groves in the municipality of Bonito, Pernambuco, Brazil. The incidence of myxomycetes on coconut palms and substrates and their composition, richness, taxonomic diversity, constancy, abundance, and seasonality of sporulation were analyzed. During direct field collections, inspections were made of the stems, leaf sheaths, inflorescence bracts, and petiole bases of 60 adult individuals. Myxomycetes were present in 80% of the coconut palms and were more abundant during the rainy season (June). A total of 128 specimens were obtained (63% from leaf sheaths, 31% from stems, 4% from petiole bases, and 2% from bracts), representing 14 species, with species/genus ratio = 2.80. Hemitrichia serpula, Physarum decipiens and Diderma effusum characterize the myxobiota. This work presents the first record of Diderma chondrioderma, Didymium clavus, Physarum crateriforme and P. roseum on C. nucifera for Brazil. The ocurrence of Didymium megalosporum in Brazil is confirmed 107 years after its first and only record in ground litter in an undefined location.
1051-P: Elevated Cord Serum Adiponectin Concentration Is Associated with Increased Risk for Fetal Overgrowth
Authors: CHEN XINHUA , WHITING JOSHUA A.
Published: May 2022

Adiponectin is an important adipokine that promotes insulin sensitivity and stimulates glucose and lipids metabolism. Whether maternal and fetal adiponectin influence fetal growth is not fully understood. We examined the association of maternal (at entry and 3rd trimester, 16 and 30 weeks of gestation) and cord serum adiponectin levels with fetal growth in a nested case-control study in 100 healthy mother (age 21.5±5 yr., BMI 25.7±7) and infant pairs selected from a large prospective cohort. The samples included large for gestational age (LGA, n=32) , small for gestational age (SGA, n=26) and appropriate for gestational age (AGA, n=42) newborns. Adiponectin levels (µg/ml) were analyzed by ELISA. Multivariate analyses adjusted for potential confounding variables were performed. Adiponectin level in cord serum was 2.75 and 3.3-fold higher than that in maternal serum at entry and 3rd trimester respectively (p<0.00for each) . Maternal and cord serum adiponectin were not significantly correlated at entry (r=-0.065, p>0.05) and in the third trimester (r=0.066, p >0.05) . Fetal adiponectin was significantly and positively correlated with infant birth weight, birth length, head and chest circumferences (r=0.254 to 0.337, p<0.to p<0.0001) . Moreover, the highest tertile of fetal adiponectin (highest tertile, >78.0) was associated with an increased risk of LGA (AOR 3.13, 95% CI 1.18, 8.31) , and a reduced risk of SGA (AOR 0.20, 95% CI 0.05, 0.77) . In contrast, maternal adiponectin levels at entry and 3rd trimester were not associated with infant birth weight or sizes (r=-0.132 to 0.146, p>0.for each) . Differences in maternal adiponectin among 3 groups of LGA, SGA and AGA were not statistically significant (p>0.05) . Our data suggest that increased cord adiponectin level is associated with an increased risk of LGA in healthy pregnant women. It may implicate that maternal and fetus adiponectin have opposite roles in regulating and maintaining a normal fetal growth.

Disclosure

X.Chen: None. J.A.Whiting: None.

Funding

National Institutes of Health (R01MD007828)
1059-P: Metabolic Trajectories from Preconception to Midpregnancy Using a Nontargeted Approach in Mothers with Gestational Diabetes Mellitus
Authors: LI LING-JUN , WANG XIMENG , CUI LIANG , ZHANG CUILIN ,   SPRESTO STUDY GROUP
Published: May 2022

The trajectories of plasma lipids and fatty acids from preconception to antenatal phases are understudied. Within a Singapore preconception and pregnancy cohort of 373 live singletons, we ascertained 35 Chinese pregnant women with gestational diabetes mellitus (GDM) according to IADPSG criteria between 24-28 weeks of gestation, and matched with 35 non-GDM Chinese controls by age and pre-pregnancy body mass index. We collected bloo samples at preconception, early (11-13 weeks) , and mid-pregnancy (18-21 weeks) . We employed OPLS-DA and logistic regression to discriminate women with and without GDM using a non-targeted approach. We applied a generalized linear mixed model in cubic spline with interaction with gestation weeks to look at metabolite trajectories across three timepoints between GDM and non-GDM matches. A total of metabolites exhibited distinctive signals from pregnant women with GDM from women without GDM in early pregnancy, such as LPE 22:6 and DHA: 22:6n3. All trajectories but one (palmitic acid) showed significant increments in preconception and mid-pregnancy phases, whereas a significant reduction in early pregnancy among GDM cases. Our data identified distinctive metabolites changes across preconception and mid-pregnancy phase among GDM subjects, and such novel findings might imply potential predictive values for incident GDM.

Disclosure

L.Li: None. X.Wang: None. L.Cui: None. C.Zhang: None. Spresto study group: n/a.

Funding

Singapore-NMRC/TCR/004-NUS/2008; NMRC/TCR/012-NUHS/2014; NMRC TA/0027/2014) .
113-LB: Oral Menin Inhibitor, BMF-219, Displays a Significant and Durable Reduction in HbA1c in a Type 2 Diabetes Mellitus Rat Model
Authors: SOMANATH PRIYANKA , MOURYA SANCHITA , LI WEIQUN , ARCHER TENLEY C. , LAW BRIAN , LU DANIEL , RUGHWANI TRIPTA , KUMAR LEKHA , KINOSHITA TAISEI , BALAKRISHNAN MINI , BUTLER THOMAS
Published: May 2022

Menin is an epigenetic regulatory protein that plays a key role in beta-cell proliferation and function, as previously demonstrated though increased beta-cell mass generation in Men1 knockout mice (Ja et al., 2021;13 (5) :e13524) . Here, we demonstrate the marked potential of an oral menin inhibitor, BMF-219, in durable glycemic control following a short course treatment in a Type 2 Diabetes Mellitus (T2DM) Zucker Diabetic Fatty Rat model. Rats were treated daily with BMF-219, liraglutide or vehicle for 28 days and monitored for an additional 28 days post-treatment. All animals tolerated BMF-219 well throughout the study. Notably, BMF-219 treatment resulted in a significant reduction in HbA1C at Day 21, which reached 3.5% absolute reduction in HbA1C versus vehicle, compared to liraglutide (1.7% reduction) at Day 29 and remained reduced throughout the entire study, including post-treatment. The high-dose arm of BMF-219 showed a strong reduction in 4-hour fasting blood glucose during the treatment up to Day 29. Both BMF-219 dose groups showed improved glycemic control by oral glucose tolerance test (OGTT) on day 25, in contrast to vehicle and liraglutide-treated animals. Additionally, insulin levels, HOMA-IR, HOMA-B, OGTT, HbA1C, and C-peptide levels measured at Day 57 across all groups will be reported. Collectively, these data demonstrate the novel long-acting potential of BMF-219 as an oral treatment for T2DM, in maintaining glycemic control after short-term dosing.

Disclosure

P. Somanath: Employee; Biomea Fusion, Inc., Stock/Shareholder; Biomea Fusion, Inc. M. Balakrishnan: Employee; Biomea Fusion, Inc., Other Relationship; Gilead Sciences, Inc., Stock/Shareholder; Biomea Fusion, Inc., Gilead Sciences, Inc. T. Butler: Employee; Biomea Fusion Inc. S. Mourya: Employee; Biomea Fusion, Stock/Shareholder; Ascendis Pharma A/S. W. Li: None. T. C. Archer: Employee; Biomea Fusion. B. Law: Stock/Shareholder; Biomea Fusion Inc., Mirum Pharmaceuticals. D. Lu: Employee; Biomea Fusion Inc., Stock/Shareholder; AbbVie Inc. T. Rughwani: None. L. Kumar: None. T. Kinoshita: None.
1158-P: The Effect of Surgical Weight Loss on Diabetic Complications in the Severely Obese
Authors: REYNOLDS EVAN L. , WATANABE MAYA , ELAFROS MELISSA , FELDMAN EVA L. , CALLAGHAN BRIAN C.
Published: May 2022

The aim of this study was to determine the effect of surgical weight loss on chronic kidney disease (CKD) , retinopathy, and cardiovascular autonomic neuropathy (CAN) in people with severe obesity.

We completed a prospective cohort study of participants with severe obesity who underwent bariatric surgery. At baseline and at 2 years following bariatric surgery, participants had outcome measurements and underwent metabolic phenotyping. The updated National Cholesterol Education Program (NCEP) criteria were used to define the metabolic syndrome (MetS) and its individual components. The primary outcome for CKD was the estimated Glomerular Filtration Rate (eGFR) , retinopathy was mean deviation on frequency doubling technology testing, and CAN was the expiration/inspiration (E/I) ratio.

Among 138 baseline participants, 80 (mean (standard deviation) age: 45.6 (11.2) years, 72.5% female) completed 2 years of follow-up. Participants lost 31.9 (17.5) kg. All metabolic syndrome components improved with the exception of blood pressure. CKD worsened (eGFR: baseline: 85.6 (19.7) , 2-year: 82.6 (23.1) , p=0.04) , retinopathy was stable (mean deviation: baseline: −1.2 (4.3) , 2-year: −1.6 (4.2) , p=0.53) , and CAN was stable (E/I ratio: baseline: 1.18 (0.12) , 2-year: 1.18 (0.11) , p=0.95) following bariatric surgery. Greater reduction in fasting glucose was associated with significant improvements to primary CKD (eGFR: point estimate (PE) : -0.22, 95% Confidence Interval (CI) : −0.38, −0.06) and retinopathy (mean deviation: PE: -0.04, 95%CI: −0.08, −0.004) , after adjusting for age, sex, and baseline BMI.

Surgical weight loss was associated with improvements in all metabolic parameters except blood pressure. Despite the improvement to metabolic risk factors, CKD significantly worsened during follow-up, whereas retinopathy and CAN outcomes remained stable. This stability may be an improvement compared to the natural progression of these conditions, however controlled trials are needed to confirm.

Disclosure

E.L.Reynolds: None. M.Watanabe: None. M.Elafros: None. E.L.Feldman: None. B.C.Callaghan: None.

Funding

The project described was supported by Grant Number P30DK020572 (MDRC) from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) . Dr. Callaghan is currently funded by a NIH NIDDK R-award (DK115687) . Dr. Reynolds was supported by NIH T32 (NS0007222) . Dr. Feldman was supported by an NIH NIDDK DP3 award (DK094292) and is currently funded by NIH NIDDK (R24082841 and R21 NS102924) and the Novo Nordisk Foundation Center for Basic Metabolic Research (NNF14°C0011633) . Dr. Reynolds, Dr. Callaghan, and Dr. Feldman receive support from the NeuroNetwork for Emerging Therapies and the A. Alfred Taubman Research Institute at the University of Michigan.
124-OR: HbA1c Variability Is Independently Associated with Lower-Extremity Amputation and Death among Patients with Diabetic Foot Ulcers
Authors: JAGANNATHAN RAM , SCHECHTER MARCOS COUTINHO , ALVAREZ JESSICA A. , BLANCO GERARDO , RAJANI RAVI , SANTAMARINA GABRIEL , UMPIERREZ GUILLERMO E. , FAYFMAN MAYA
Published: May 2022

Background: Higher HbA1c on admission is associated with increased amputation risk in patients with diabetic foot ulcers (DFUs) ; however, the impact of long-term glycemic control and glycemic variability after hospital discharge on amputation risk is unclear.

Methods: We performed retrospective analyses of hospitalized patients with a DFU who were followed for >1 year after index admission with at least two HbA1c measurements and > 1-year follow-up (n=479) . Using multivariable logistic regression analysis, we examined the associations of HbA1c measures [HbA1c nadir change (difference between the baseline HbA1c and the single lowest prospective HbA1c level during the follow-up) , standard deviation (SD-HbA1c) , mean HbA1c change, and HbA1c variability score (HVS) ] with a composite outcome [minor and major lower extremity amputations (LEA) and mortality].

Results: The median age was 55.3 (IQR: 47.9, 62.8) years. During a mean follow-up of 2.4 years, 250 (52.2%) patients had a LEA or death [minor LEA: 116 (24.2%) ; major LEA: 113 (23.4%) ; death: 21 (4.4%) ]. In the fully adjusted model, HbA1c variability metrics were significantly associated with higher LEA and/or death rates, except HVS (Table) .

Conclusion: Our findings indicate that visit-to-visit HbA1c variability, especially HbA1c nadir change, and SD-HbA1c are independent biomarkers of LEA risk in patients with DFU.

Disclosure

R.Jagannathan: None. M.Schechter: None. J.A.Alvarez: None. G.Blanco: None. R.Rajani: None. G.Santamarina: None. G.E.Umpierrez: Research Support; AstraZeneca, Dexcom, Inc., Novo Nordisk. M.Fayfman: None.

Funding

Emory Medical Care Foundation to MCS and MF
1257-P: Associations of Five-Year Type 1 Diabetes (T1D) Risk with Predictors Using Cross-Sample Validation
Authors: ISMAIL HEBA M. , CUTHBERTSON DAVID D. , ATKINSON MARK A. , REDONDO MARIA J. , SOSENKO JAY ,   TYPE 1 DIABETES TRIALNET
Published: May 2022

We studied 5-yr T1D risk associations using a series of risk factors in an autoantibody positive population of 6,020 in the TrialNet Pathway to Prevention study (PTP) study. We used data from 25 subgroups developed from 5 AUC glucose (<115;115-<130;130-<145;145-<160; ≥160 mg/dl) and 5 AUC C-peptide (<3.5;3.5-<5.0;5.0-<6.5;6.50-<8.0; ≥8.0 ng/ml) categories from baseline OGTT data. Subgroup boundaries were set to provide quantitative power for proper statistical analysis (range: 138 to 487) . We assessed 5-yr T1D risk associations with risk factors among the 25 subgroups using correlation coefficients and linear regression analysis (slope: 5-yr risk/risk factor prevalence) . The table shows the strongest correlation of 5-yr T1D risk with IA-2A (r=0.96) . This was consistent in split sample analyses, as were the linear regression indices (Sample 1 vs. Sample 2: r=0.96 vs. 0.93; intercept=-0.186 vs. -0.228; slope=0.014 vs. 0.015) . Using the regression indices for a cross-sample validation (i.e., predicting 5-yr risk for one sample using its IA-2A prevalence and the other sample's regression indices) , the predicted/actual 5-yr risk was 0.27/0.26 for Sample 1 and 0.27/0.23 for Sample 2.

In summary, in PTP subgroups, 5-yr T1D risk correlated strongly with IA-2A. Further, regression indices predicted 5-yr T1D risk in cross-sample validation, suggesting a tight linkage between active β-cell decline and IA-2A.

Disclosure

H.M.Ismail: n/a. D.D.Cuthbertson: None. M.A.Atkinson: None. M.J.Redondo: Advisory Panel; Provention Bio, Inc. J.Sosenko: None. Type 1 diabetes trialnet: n/a.

Funding

NIH
13-OR: Cystic Fibrosis Donors Exhibit Striking Decrease in Pancreatic Islet and Exocrine Capillaries
Authors: CASTILLO JOSEPH J. , APLIN ALFRED , AKTER REHANA , HULL-MEICHLE REBECCA L.
Published: May 2022

Glucose intolerance and insulin deficiency are common features of cystic fibrosis (CF) , with nearly half of adult CF patients developing CF-related diabetes (CFRD) , but the underlying pathophysiology remains poorly understood. Extensive destruction of the exocrine pancreas occurs in most CF patients. However, islets are still readily detectable, suggesting β cell loss is not the major driver of impaired insulin release. Islets are normally highly vascularized, and islet capillaries are the source of key growth factors that maintain β cell health and function. Islet capillary morphology is altered in type 1 and type 2 diabetes, with increased capillary density and/or vessel thickening being observed. In the present study we aimed to determine whether islet capillaries are also disrupted in CF/CFRD. Pancreas sections (8 control and 8 CF/CFRD, age-matched) were stained for CD31, a marker of vascular endothelial cells. Islets in microscopy images were manually identified (17.8±2.8[SEM] per sample) and CD31-positive area within islet and exocrine was quantified. Mean islet cross-sectional area did not significantly differ between CF and non-CF pancreas specimens. CD31 positive area, expressed as a fraction of islet area, was significantly decreased in CF pancreas specimens (2.8±0.9% vs. 6.1±1.2%; p=0.05) . Islet capillary density (the number of CD31+ objects normalized to islet area) was also decreased (0.88±0.17x103/μm2 vs. 3.8±0.57x103/μm2; p=0.0004) , as was exocrine tissue CD31 positive area (0.17±0.03% vs. 1.5±0.23%; p<0.0001) . Our data demonstrate a significant deficit in islet and pancreatic vascularity in CF/CFRD. This contrasts markedly with the increase in islet capillary density seen in both T1D and T2D and underscores the presence of distinct features of islet morphology that characterize CF. Given that islet capillaries support β-cell function and survival, their loss likely contributes to impaired β-cell function.

Disclosure

J.J.Castillo: None. A.Aplin: None. R.Akter: None. R.L.Hull-meichle: Research Support; Casma Therapeutics.

Funding

Cystic Fibrosis Foundation Fellowship (CASTIL20F0)
1304-P: Quantification of Preproinsulin and Insulin Isoforms Derived from Upstream Open Reading Frames in Human Clinical Samples by Selected Reaction Monitoring Assay
Authors: LIU QING-RONG , ZHU MIN , GHOSH PARITOSH , CHIA CHEE W. , EGAN JOSEPHINE M.
Published: May 2022

We recently uncovered a novel human proinsulin containing a amino-acid Cα-peptide and upstream open reading frame (uORF) isoforms whose transcription is initiated from an alternative INS promoter upstream of the conventional INS promoter (Liu et al, 2021, Diabetes, PMID: 34649926) . Post-translational protease processing of preproinsulin is reported to be involved in the pathogenesis of diabetes. However, there are no sensitive and specific assays to quantify unprocessed preproinsulin and insulin originating from uORFs in clinical samples. Hence, we developed an LC-MS/MS based Selected Reaction Monitoring (SRM) assay to quantify the fragments of processed and unprocessed signal peptide in plasma, pancreatic islets, cerebrospinal fluid (CSF) , and brain. Trypsinization of insulin B-chain generates two peptides: peptide-B1 (pep-B1: FVNQHLCGSHLVEALYLVCGER) that requires cleavage by signal peptidase (SPase) , and peptide-B2 (GFFYTPK) that does not require SPase. As a result, the pep-B1 derived from preproinsulin cannot be detected if the signal peptide fails to be cleaved by SPase. Therefore, the pep-B1 could serve as a surrogate for preproinsulin since its quantity is correlated with the signal peptide cleavage efficiency. We also developed an SRM peptide panel to detect and measure insulin derived from uORF isoforms. Our SRM assay allows for measurement of insulin A- and B-chains separately in plasma samples, and levels highly correlate with ELISA after a glucose stimulus to secretion. We detected more unconventional uORF-derived insulin in CSF and cerebrum in comparison with plasma and islets. Furthermore, we found that uORF levels were significantly altered in middle temporal gyrus (MTG) of postmortem brains of Alzheimer Disease patients compared to control MTGs. The newly developed SRM assay could serve to determine preproinsulin and insulin uORF isoforms in clinical biofluid and tissue samples.

Disclosure

Q.Liu: None. M.Zhu: None. P.Ghosh: None. C.W.Chia: None. J.M.Egan: None.

Funding

This research was supported entirely by the Intramural Research Program of the NIH, National Institute on Aging
1313-P: Short-Chain Fatty Acids Decrease Food Intake through Free Fatty Acid Receptors in the Brain
Authors: LUO PEI , XU PINGWEN , FENG BING , YE HUI , PATEL NIRALI , LAYDEN BRIAN T. , HE YANLIN , KOTA MAYA , DIXIT DEVIN , ANTONY NIMISHA , CARRILLO-SÁENZ LESLIE , TORRES IRIZARRY VALERIA C. , IBRAHIMI LUCAS , SCHAUL SARAH
Published: May 2022

The influence of gut bacteria on host energy homeostasis is increasingly recognized, but mechanistic links are lacking. The gut microbiota digests and ferments nutrients, which result in short-chain fatty acids (SCFAs) . The body senses these nutrients in large part through free fatty acid receptors 2 (FFA2) and 3 (FFA3) . Accumulating evidence indicates that the gut microbiota/SCFAs interact with the central nervous system (CNS) to regulate brain metabolic function. Consistently, we found that a single acute intracerebroventricular (ICV) injection of acetate (ACE) , propionate (PRO) , or butyrate (BUT) dose-dependently inhibited food intake in an FFA2/3-dependent manner. The reduced food intake induced by ACE, PRO, or BUT was attributed to decreased meal size or increased intermeal interval. These regulatory effects on meal patterns were blunted in FFA2 and FFA3 double-receptor knockout mice, suggesting a mediating role of brain FFA2/3. Interestingly, RNAscope analysis showed that FFA3 but not FFA2 highly expressed in the cerebellar granule neurons. Using brain slice patch-clamp, we consistently showed that PRO or FFA3-selective agonists inhibited these granule neurons. Notably, the hyperpolarization effects of PRO on cerebellar granule neurons were blocked by pertussis toxin (PTX) , a G-protein coupled receptor subunit Gi/o blocker, further supporting an FFA3-Gi/o-mediated inhibition on granule neurons. These results suggest a model that SCFAs inhibit food intake through FFA3 expressed by the cerebellar granule neurons.

Key words: SCFA; Brain; FFA3

Disclosure

P. Luo: None. P. Xu: None. H. Ye: None. B.T. Layden: None. Y. He: None. V.C. Torres Irizarry: None.
1324-P: Short-Term Effects of Glycemia-Lowering Medications on ß-Cell Function in the GRADE Study
Authors: RASOULI NEDA , ALBU JEANINE , COHEN ROBERT M. , DEFRONZO RALPH A. , DIAZ ELSA , GHOSH ALOKANANDA , LUCHSINGER JOSE A. , MCGILL JANET B. , KASSEM LAURE SAYYED , SIVITZ WILLIAM , TAMBORLANE WILLIAM V. , UTZSCHNEIDER KRISTINA , YOUNES NAJI , KAHN STEVEN E. ,   GRADE RESEARCH GROUP
Published: May 2022

Therapies that preserve β-cell function and enhance glycemic control in type 2 diabetes are of great value. We examined β-cell function in GRADE participants after one year of intervention with insulin glargine U-100, glimepiride, liraglutide or sitagliptin. Participants who remained on originally assigned medication and had complete OGTT data at baseline and Year 1 were analyzed (n=3342 of 5047 initially randomized) . OGTT derived β-cell responses were measured as the ratio of the increment of C-peptide to glucose in the first 30 minutes (CPI) and over 120 minutes (CP/G AUC) . At baseline, age (57.7±9.7 y) , sex (63.5% male) , race (66.8% White) , BMI (34.2±6.7 kg/m2) , fasting C-peptide (1.3±0.5 nmol/L) , HOMA-B (87±35.2 %) , CPI (0.08±0.nmol/mg) and CP/G AUC (1.1±0.6 nmol/mg) did not differ by treatment group. At Year 1, measures of β-cell function were different by treatment groups (Table) . After pairwise analysis, glargine had the lowest fasting C-peptide while CP/G AUC was highest in the liraglutide group. When tested for treatment heterogeneity across subgroups, participants with longer duration of diabetes had smaller increases in CPI and CP/G AUC. Decreased fasting C-peptide by glargine is likely due to lower endogenous insulin secretion in the setting of exogenous insulin. Improved β-cell responses with liraglutide may indicate better β-cell function during the first year of treatment.

Disclosure

N. Rasouli: Advisory Panel; Eli Lilly and Company, Novo Nordisk, Sanofi. Research Support; Allergan, Eli Lilly and Company, Novo Nordisk. J. Albu: None. R.M. Cohen: Research Support; Dexcom, Inc. R.A. DeFronzo: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Intarcia Therapeutics, Inc., Novo Nordisk. Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Merck & Co., Inc. Speaker’s Bureau; AstraZeneca. E. Diaz: None. A. Ghosh: None. J.A. Luchsinger: None. J.B. McGill: Advisory Panel; Gilead Sciences, Inc., Lilly Diabetes, MannKind Corporation, Novo Nordisk A/S, Provention Bio, Inc., Salix Pharmaceuticals. Consultant; Bayer AG, Boehringer Ingelheim International GmbH. Research Support; Dexcom, Inc., Novo Nordisk. L. Sayyed Kassem: None. W.V. Tamborlane: Consultant; AstraZeneca, Boehringer Ingelheim International GmbH, Medtronic, Novo Nordisk, Sanofi, Takeda Pharmaceutical Company Limited. K. Utzschneider: Consultant; Nevro Corp. N. Younes: None. S.E. Kahn: Advisory Panel; Bayer AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Intarcia Therapeutics, Inc., Merck & Co., Inc., Novo Nordisk, Pfizer Inc.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (U01DK098246, U34-DK-088043)
1335-P: Deciphering Liver Glycome Regulation by the PGC-1/FN3K Axis
Authors: SAAR EFRAT GLICK , DAIME YOHANNIES G. , TIROSH AMIR , MINSKY NERI
Published: May 2022

Diabetes in general, and specifically in the context of obesity, is characterized by hyperglycemia resulting in non-enzymatic glycation of proteins, a key event in the pathophysiology of diabetes and its chronic complications. Yet, the full scope of molecular targets for glycation, particularly in liver, is incompletely understood. De-glycation, which removes the attached sugars, is controlled intracellularly by fructosamine-3-kinase (FN3K) , a kinase that phosphorylates the attached sugar and has been proposed to have a protective role against the deleterious effects of glycation related to diabetes. However, FN3K has been suggested to be ubiquitously expressed and to act as a constitutive housekeeping gene. Furthermore, whether intracellular de-glycation is regulated in physiological contexts and what factors are involved in its regulation remain unknown. Our data identify that regulation of protein glycation in liver is controlled by the key metabolic regulators PGC-1s (PGC-1alpha and PGC-1beta) in response to metabolic cues, particularly in the fed state. Liver-specific deletion of PGC-1s results in reduction of Fn3k expression and concomitant increase in specific protein glycation. In accordance, overexpression of PGC-1alpha in liver-derived cells induces Fn3k and a reduction in protein glycation. Purification of glycated proteins followed by mass spectrometric analysis reveals significant alterations in intracellular protein glycation in response to PGC1-alpha expression. Mechanistically, PGC-1alpha effect on Fn3k involves the activity of the transcription factor Foxo1. Thus, in liver, fasting and re-feeding govern intracellular protein glycation via PGC-1 dependent induction of FN3K. Our work reveals the scope and dynamic nature of the liver glycome, establishing the PGC1/FN3K axis as a key regulator of protein glycation.

Disclosure

E.Glick saar: None. Y.G.Daime: None. A.Tirosh: Advisory Panel; Abbott Diagnostics, AstraZeneca, Boehringer Ingelheim International GmbH, Merck & Co., Inc., Novo Nordisk, Sanofi, Consultant; Bayer AG, DreaMed Diabetes, Ltd., Research Support; Medtronic, Speaker’s Bureau; Eli Lilly and Company. N.Minsky: None.
1374-P: In Type 2 Diabetes, the Exocrine Pancreas Has Greater Fibrosis, Fat, Metaplastic Changes, and Microangiopathy
Authors: WRIGHT JORDAN J. , ESKAROS ADEL , WINDON ANNIKA L. , SAUNDERS DIANE C. , BOTTINO RITA ,   HUMAN PANCREAS ANALYSIS PROGRAM, BRISSOVA MARCELA , POWERS ALVIN C.
Published: May 2022

Type 2 diabetes (T2D) is associated with increased risk of pancreatic cancer. Our knowledge of exocrine pancreas histopathology in T2D is incomplete. To determine whether T2D is associated with changes in the pancreatic exocrine compartment, we analyzed tissue sections from the pancreatic head, body, and tail of 25 T2D donors (age 51 ± yrs, duration 3.4 ± 2.6 yrs, 9/25 on insulin, BMI 35.5 ± 6.3, A1c 7.5 ± 1.5%) and 26 non-diabetic donors (ND; age 41 ± yrs, BMI 28.7 ± 5.0, A1c 5.3 ± 0.4%) using histochemistry, immunofluorescence, and CODEX multiplexed imaging with automated quantitation and manual review by two pathologists. Compared to ND, T2D pancreata were larger (113.3 ± 6.9 vs. 93.8 ± 6.7 g, p<0.05) and had more exocrine fibrosis (29.4 ± 1.6 vs. 17.3 ± 2.7% area, p<0.01) , inter- and intra-lobular fat (14.6 ± 2.0 vs. 7.6 ± 1.5% area, p<0.01) , acinar-to-ductal metaplasia (ADM; 1.4 ± 0.3 vs. 0.3 ± 0.1 positive lobules/section, p<0.01) , pancreatic intraepithelial neoplasia (PanIN; present in 40.0 vs. 14.8%, p<0.05) , and small vessel angiopathy (7.0 ± 0.5 vs. 3.6 ± 0.6 combined score, p<0.001) . In contrast, exocrine tissue from 16 donors with type 1 diabetes (T1D; age 23 ± 7 yrs, duration 11.5 ± 8.2 years, BMI 23.7 ± 5.4, A1c 9.1 ± 1.7%) had no increase in ADM, PanIN, fat or angiopathy. Though similar in severity, T2D fibrosis was predominantly intralobular, while T1D was interlobular, perivascular, and periductal. T2D tissues with greater fibrosis had more activated stellate cells compared to low fibrosis tissues (5.6 ± 1.1 vs. 1.0 ± 0.2% area, p<0.05) . Endothelial cell density, shape, and size and macrophage abundance and phenotype were similar in T2D and ND, while T cells were greater in T2D (4.1 ± 1.6 vs. 3.9 ± 1.8% of cells, p<0.05) with no change in subtype or activation. Thus, T2D is associated with marked changes in the pancreatic exocrine compartment. Whether these exocrine changes contribute to islet dysfunction or influence the risk of pancreatic cancer in T2D is unknown.

Disclosure

J.J.Wright: None. A.Eskaros: None. A.L.Windon: None. D.C.Saunders: None. R.Bottino: Employee; Imagine Pharma. Human pancreas analysis program: n/a. M.Brissova: None. A.C.Powers: None.