bluuebunny/crossref_metadata_2025_split huggingface dataset:
436-P: Reducing Autoinflammation: The Impact of T-Cell Deficiency on Atherosclerosis
Authors: SHEPHERD ALYSSA J. , YUSSMAN MARTIN , WAGNER DAVID H. , VAITAITIS JR., GISELA M. 
Published: May 2022

Type 1 diabetes (T1D) , a prototypic autoimmune disease, creates several serious complications of which atherosclerosis is the major co-morbid condition. Atherosclerosis is defined by arterial plaque deposition due to coagulation blood products, lipid deposition, and inflammation. The latter has been known for more than a decade but only recently have inflammatory mediators proven to be a beneficial target once traditional treatment has been exhausted. T-cell mediators associated with the CD40-CD154 inflammatory dyad are found in autoimmune diseases such as T1D and rheumatoid arthritis and may be a cause of the added atherosclerotic risk which these disease states maintain. This study seeks to explore the role of T cells in atherogenesis through the use of pro-atherogenic ApoE-/- mice bred to create T cell deficiency (ApoE-/- TCRα-/-) for analysis of the overall effect of T cells in atherogenesis. Mice are sacrificed at 8 months of age and dissected to obtain the aortas and hearts. The aorta is used for en-face Sudan IV staining analysis while serial aortic valve cross sections are used to characterize the lesion in terms of area and content. Analyses of aortic valve cross sections (A-D) and whole aortas (E-F) of this novel model not only demonstrated a significant reduction in overall plaque, but also revealed a change in plaque composition due to T cell deficiency. Future aims are to define the specific subset of pathogenic T cells.

Disclosure
A.J.Shepherd: None. M.Yussman: None. D.H.Wagner: Other Relationship; Op-T, LLC. G.M.Vaitaitis: None.

Funding
National Institutes of Health (4R42DK115296-02)
454-P: Association between Insulin and C-Reactive Protein: Data from Athletes and Coronary Angiography Patients
Authors: LEIHERER ANDREAS , RINDERER MARTIN , MUENDLEIN AXEL , SAELY CHRISTOPH H. , MADER ARTHUR , SPRENGER LUKAS , MAECHLER MAXIMILIAN , VONBANK ALEXANDER , LARCHER BARBARA , FRAUNBERGER PETER , SOHM MARC , PHILIPPE MARC , DREXEL HEINZ 
Published: May 2022

A better understanding of the relationship between insulin and inflammation may have important implications for the treatment and prevention of diabetes. Chronic inflammation and diabetes are associated with coronary artery disease (CAD) . That said, many studies found no correlation between insulin and C-reactive protein (CRP) , the most common marker of chronic inflammation. We hypothesize here that the association of insulin and CRP may differ in different patient groups and may be masked by factors such as age, fitness or diseases, in particular established CAD. We thus evaluated the correlates of insulin and CRP among healthy professional athletes (Group 1, mean age = 24 years (ranging from 18-35 years) , n=59) , and patients undergoing coronary angiography (27-88 years, n=1574) who were further divided into younger (&lt;60 years) patients without sign. CAD (Group 2, mean age = 52 years, n=258) , younger patients with sign. CAD (Group 3, mean age = 52, n=287) and older (≥60 years) patients without sign. CAD (Group 4, mean age 69, n=407) as well as older patients with sign. CAD (Group 5, mean age 70, n=622) . CRP and insulin were positively correlated in athletes (r1=0.544, p&lt;0.001) and in patients without sign. CAD (r2=0.194, p=0.002 and r4=0.134, p=0.007) but not in patients with sign. CAD (r3=-0.001, p=0.981 and r5=0.000, p=0.955) . In multivariate models including covariates BMI and age, CRP and insulin remained significantly associated in athletes (T1=4.7, p&lt;0.001) and in patients without sign. CAD (T2+4=3.3, p=0.001) , but not in those with sign. CAD (T3+5=0.0, p=0.997) . We conclude that CRP and insulin correlate in young and fit subjects but also in older subjects who do not have sign. CAD. The presence of CAD may abrogate the association between inflammation and insulin, potentially due to the inflammatory state of atherosclerosis. This appears worthwhile to be considered in future screening and treatment approaches.

Disclosure
A.Leiherer: None. P.Fraunberger: None. M.Sohm: None. M.Philippe: None. H.Drexel: None. M.Rinderer: None. A.Muendlein: None. C.H.Saely: None. A.Mader: None. L.Sprenger: None. M.Maechler: None. A.Vonbank: None. B.Larcher: None.
457-P: Increase in Functional Connectivity of the Thalamus to the Primary Somatosensory Cortex and Insular Cortex after Withdrawal of Neuropathic Pain Medication: A Potential Biomarker of Painful-DPN
Authors: SLOAN GORDON P. , SELVARAJAH DINESH , TEH KEVIN , TESFAYE SOLOMON 
Published: May 2022

Aims: Altered functional connectivity has been identified in key brain regions involved in somatosensory perception in patients with painful diabetic peripheral neuropathy (painful-DPN) , using resting state functional-magnetic resonance imaging (fMRI) . This study aimed to examine the impact of neuropathic pain treatments on these regions.
Methods: Fifteen participants with Painful-DPN enrolled in the OPTION-DM clinical trial underwent underwent fMRI imaging using 3T when the participants were on maximum tolerated medication (Treatment Scan) and one week after medication washout (Washout Scan) . The data was analysed using Conn Functional Connectivity Toolbox in SPM.
Results: There was a significant increase in Pain Numeric Rating Scale (NRS) from Treatment Scan (4.0 ± 2.1) to the Washout Scan (6.1 ± 2.4, p=0.044) with a corresponding rise in functional connectivity between the Primary Somatosensory Cortex (S1) and the Thalamus, and the Insular Cortex and Thalamus (p=0.041) . There was a significant difference in the change between scans in S1 - Thalamic functional connectivity in participants with Severe-Pain (NRS ≥8 at baseline: -0.372 ± 0.275) compared to participants with Moderate-Pain (NRS ≤7: -0.051 ± 0.180, p=0.035) . The change in S1-Thalamic connectivity also correlated with baseline pain (r -0.585, p=0.022) and the difference in NRS at the Treatment Scan and Baseline pain (r -0.513, p=0.050) .
Conclusions: On neuropathic pain medication withdrawal there is an increase S1 - Thalamus and Insular Cortex - Thalamus functional connectivity. Moreover, the change in S1 - Thalamus functional connectivity from the Treatment Scan to Withdrawal Scan differentiated participants with high and low baseline neuropathic pain. This study demonstrates that thalamic functional connectivity to the S1 and Insular Cortex has the potential to act as a biomarker of painful-DPN.

Disclosure
G.P.Sloan: None. D.Selvarajah: None. K.Teh: None. S.Tesfaye: Advisory Panel; Astellas Pharma Inc., Bayer AG, Grünenthal Group, Nevro Corp., Wörwag Pharma GmbH & Co. KG, Speaker's Bureau; Eva Pharma, Pfizer Inc., Viatris Inc.
459-P: Effects of Liraglutide on Somatic Nerve Function in Subjects with Type 2 Diabetes
Authors: CASELLINI CAROLINA M. , PARSON HENRI , BAILEY MICHAEL D. , SIRAJ ELIAS S. 
Published: May 2022

Background: Preclinical data has shown that GLP-1 receptor agonists play a role in nerve regeneration and repair. However, few studies have investigated the effects of these compounds on nerve function in humans. The aim of this study was to examine the effect of Liraglutide (Lira) on somatic nerve function in patients with type 2 diabetes.
Methods: Randomized, double-blind, placebo-controlled study of Lira 1.8 mg daily for 52 weeks. All participants were evaluated with the following somatic nerve function tests: Utah Early Neuropathy Scale (UENS) , quantitative sensory testing (QST) for cold and warm perception thresholds (Q-Sense v6.0.13.1; Medoc - Minneapolis, MN) , nerve conduction studies (NCS) (Sierra Summit System; Cadwell Industries - Kennewick, WA) and in vivo corneal confocal microscopy (CCM) to measure corneal nerve fiber density, branching and length (Tomograph III; Heidelberg Engineering - Smithfield, Rhode Island)
Results: We randomized 44 subjects (21 to Lira and 23 to pb) . Baseline characteristics were similar. Main results are shown in Table 1. In both groups, there was no significant change on UENS, QSTs, NCS and CCM measures after 1 year of treatment. The results also were not significantly different between the groups.
Conclusions: This study did not show improvements in somatic nerve function after 52 weeks of treatment with Lira. The small sample size may have contributed to the negative result.

Disclosure
C.M.Casellini: Advisory Panel; Nevro Corp. H.Parson: None. M.D.Bailey: None. E.S.Siraj: Consultant; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Research Support; Novo Nordisk.

Funding
Novo Nordisk (Grant#15-12-FB-0218)
464-P: Detecting Diabetic Peripheral Neuropathy Utilizing Thermoregulation of the Plantar Foot
Authors: SOLIZ PETER , DURAN-VALDEZ ELIZABETH , BANCROFT ANNA P. , TANG GUANLIN , SCHADE DAVID S. , VIJAYAMOHANAN JAYAKRISHNAN 
Published: May 2022

Purpose: To demonstrate thermal features of the foot in diabetic subjects without known peripheral neuropathy.
Background: Assessment of thermoregulation of the foot in patients diagnosed with diabetes identifies those predisposed to foot ulcer and amputation.
Methods: The clinical study of the thermoregulation of the microvascular processes of the plantar foot included 100 subjects with diabetes ages 35 to 76. Subjects underwent a complete clinical exam and nerve conduction study. Thermal imaging with a portable device followed a standard procedure for cooling of the plantar foot, followed by video imaging of the plantar surface during re-warming. The reference standard for neuropathy was a nerve conduction study. Features included: Initial temperature; temperature after cold provocation; and recovery temperatures.
Results: The figure shows the 6 standard regions studied. The temperature after cooling for the normal subject was 16 deg C with a recovery temperature of 6 to 8 deg C after 400 s. For the subject with neuropathy the temperature after cooling dropped only to 18 deg C and recovered 2 to 4 deg C. Using these features, the sensitivity was 85% sensitivity and 70% specificity.
Conclusion: Quantification of thermoregulation of the foot provides a new and non-invasive assessment of diabetic peripheral neuropathy in patients with diabetes. Identification of these at-risk patients may prevent amputation.

Disclosure
P.Soliz: None. E.Duran-valdez: None. A.P.Bancroft: None. G.Tang: None. D.S.Schade: Consultant; AbbVie Inc. J.Vijayamohanan: None.

Funding
NIH 2R44DK104578-04A1
465-P: AGE Precursor Methylglyoxal May Result in Behavioral Pattern of Neurological Disorders in Animal Mouse Model
Authors: YUE KEVIN 
Published: May 2022

Purpose of the study: Diabetes mellitus (DM) is characterized by chronic hyperglycemia and diabeticcomplications. Impairment in neuropsychological functioning in DM patients is shownin clinical studies. Patients with DM have a higher risk of developing neurologicaldisorders, including Parkinson’s disease (PD) , depression, and anxiety. Symptoms ofthese diseases are observed in diabetic animal models and in population-based studies.DM-induced activation of stress responses in the central nervous system (CNS) such asoxidative stress and neuroinflammation may lead to various neurological disorders.Abnormal accumulation of methylglyoxal (MG) , one of the most reactive advancedglycation end-product (AGE) precursors, is found in the serum of DM patients. As MGis reported to induce brain cells impairment in the CNS, the effect of MG leading tosubsequent symptoms of the three neurological disorders was investigated.
Methods: C57BL/6 mice were treated with MG solution (60mg/kg) or sham control byintraperitoneal injection for weeks. Rotarod test, open-field test (OFT) , and forcedswim test (FST) were used to examine the motor coordination, anxiety-like behavior,and depressive-like behavior of mice respectively. Corresponding parameters of thetests were measured and recorded.
Summary of the results: In the rotarod test, significantly reduced latency to fall off was observed in the MG-treated group (74.1 ± 5.33) than that in the control group (92.9 ± 5.80) . In the OFT,significantly reduced total traveled distance (285 ± 1.01) was observed in the MG-treated group than that in the control group (13.4 ± 1.48) . In the FST, significantlyincreased percentage of immobile time was observed in the MG-treated group (77.6 ±2.19) than that in the control group (68.7 ± 2.42) .
Conclusions: MG could induce symptoms of PD, depression, and anxiety in mice. MG may play arole in the dysfunction of brain cells and dysregulation of CNS resulting in neurologicaldisorders

Disclosure
K.Yue: None.
466-P: Changes in Oral and Intestinal Bacterial Flora Associated with Pain Thresholds
Authors: KUDOH KAZUHIRO , TAKEUCHI YUKI , OSONOI SHO , SASAKI TAKANORI , OGASAWARA SAORI , YAGIHASHI SOROKU , MIZUKAMI HIROKI 
Published: May 2022

Small fiber neuropathy (SFN) manifests from the early stages of diabetic polyneuropathy. Changes in the oral and intestinal bacterial flora are known to be associated with the onset and progression of diabetes and its complications. However, correlation between SFN and each bacterial flora has not yet been investigated. In the 2018 Iwaki health promotion project, which is a local health promotion study in Aomori prefecture, 1037 participants (431 males and 6females including 814 non-glucose metabolism disorders, 143 fasting hyperglycemia (IFG) , and 80 type 2 diabetic cases (DM) , were evaluated. SFN was evaluated by the pain threshold evoked by intraepidermal electrical stimulation (PINT) . A PINT value of 0.or less was designated as Pint-L, and otherwise was designated as Pint-H. DNA was isolated from saliva and feces and relative bacterial abundance was determined with a next-generation sequencer. Bacteria that account for 1% or more of all bacteria were examined. PINT was significantly increased in IFG (0.12 ± 0.11mA) and DM (0.15 ± 0.13mA) compared to healthy subjects (0.± 0.08mA) (p&lt;0.vs. IFG, p &lt;0.vs. DM) . No significant difference was found depending on the PINT value in the bacteria flora of oral cavity. There were significant differences of gut bacterial flor in α and β-diversity (p&lt;0.05) and principal component analysis (p &lt;0.01) depending on the PINT value. The genus Bacteroides was significantly higher in PINT-H than in PINT-L (p&lt;0.01) . After IFG and DM cases were excluded, a significant difference was maintained. The amount of bacteroides was significantly correlated with age, abdominal circumference, fasting blood glucose, HbA1c (p&lt;0.001) , BMI and PINT value (p &lt;0.05) . In the multiple regression analysis adjusted for these factors, PINT was significantly correlated with the amount of Bacteroides (β = -0.089, p = 0.026) . Our results suggest that the gut Bacteroides may correlate with SFN. The involvement of deterioration of glucose metabolism may not be high in this correlation.

Disclosure
K.Kudoh: None. Y.Takeuchi: None. S.Osonoi: None. T.Sasaki: None. S.Ogasawara: None. S.Yagihashi: None. H.Mizukami: None.
48-OR: Barriers to Follow-Up Specialized Eye Care following Retinopathy Identification with Traditional vs. Autonomous Artificial Intelligence (AI) Camera
Authors: WAHL MATTHEW , KIANI RABIA , NEUBERGER JULIE , WILSON BONNIE , HARTNETT MARY ELIZABETH , FISHER SIMON 
Published: May 2022

Point-of-care retinal imaging is effective at identifying diabetic retinopathy. However, appropriate follow-up, referral, and access to specialized eye care remains a barrier for the treatment of identified eye disease. We tested the hypothesis that rapid results and immediate referrals afforded by use of an automated diabetic retinopathy screening platform with AI technology (EyeArt) would result in greater patient follow up with ophthalmology specialists as compared to “traditional” tele-retinal screening (images acquired in clinic and transmitted electronically for interpretation by a vitreoretinal specialist) . All images were acquired during a patient’s regularly scheduled diabetes clinic visit. With traditional tele-retinal screening, the average turnaround time to patient notification of findings was days. Among the 357 patients that underwent traditional screening, 42 (12%) were found to have referable (more-than-mild) retinopathy, and of these, 32 (76%) followed up in ophthalmology clinic. In contrast, the fully autonomous diabetic retinopathy screening platform using AI technology provided an immediate assessment on the presence of retinopathy (within 60 seconds of photo acquisition) . Patients were given this point-of-care summary of their eye-exam findings. When indicated, an ophthalmology referral was ordered and patients were provided with contact information for the ophthalmology office. Of the 81 patients screened with AI technology, 22 (27%) had referable retinopathy detected, 15 (68%) of whom followed up in ophthalmology clinic. The higher detection rate with AI screening raises the question of “overcalling” the presence of disease. We conclude that although AI screening offers immediate results allowing for immediate ophthalmology referral, there remains a substantial barrier to ophthalmology follow up after a positive retinopathy screen identified by either screening method.

Disclosure
M.Wahl: None. R.Kiani: None. J.Neuberger: None. B.Wilson: None. M.Hartnett: None. S.Fisher: None.
483-P: Predictors of Major Adverse Lower Limb Events for Chronic Arterial Trophic Disorders
Authors: VOSGIN-DINCLAUX VALÉRIAN , MOHAMMEDI KAMEL , CARADU CAROLINE 
Published: May 2022

Background: Peripheral arterial disease (PAD) affects more than 200 million people with an ever-increasing prevalence. Faced with this public health issue, it seems crucial to take an interest in PAD management. In this study, we evaluated the predictors of major adverse lower limb events (MALEs) and wound healing following revascularization for chronic arterial trophic disorders in people with and without diabetes.
Methods: This retrospective study included all patients with Rutherford-Becker stage 5 or 6 who required a minor amputation in combination with a revascularization procedure in our vascular surgery department at Bordeaux University Hospital, from January 2016 to December 2018. The primary endpoint was MALEs. The secondary endpoints were wound healing at 6 months and 2 years, in-hospital and all-cause mortality.
Results: We included 241 patients, 180 with diabetes (74,7%) , with an average age of 74 years, 79,7% men. According to the Wound, Ischemia and foot Infection classification, 95,9% were ranked clinical stage 4, and to the TransAtlantic Inter-Society Consensus for the management of PAD (TASC) below-the-knee classification, 50,7% were stage C/D. Among patients with diabetes, 63,3% had post-operative uncontrolled diabetes. One-hundred seven MALEs occurred during 2-year follow-up (estimated rate of patients free of MALEs 48,7%, 95% CI: 41,7-55,4) , 78 MALEs in patients with diabetes. Revascularization failure predicted the occurrence of MALEs in multivariate analysis, while the lack of revascularization option predicted major amputation. Wound healing was adversely affected by haemodialysis, TASC C/D below-the-knee lesions, the number of bacteria, and reocclusion of the target artery. The in-hospital mortality rate was 5,4% and the overall 2-year mortality rate was 22,8%.
Conclusion: This study highlights the necessity to provide optimal revascularization associated with comprehensive medical care using multidisciplinary approaches to those patients affected by PAD.

Disclosure
V.Vosgin-dinclaux: None. K.Mohammedi: Board Member; Lilly, Novo Nordisk, Sanofi, Research Support; Cyclerion Therapeutics, Inc., Speaker's Bureau; Abbott, AstraZeneca. C.Caradu: None.
484-P: Uncoupling of IL-1beta and VEGF-A Signaling Axis Contributes to Impaired Arteriogenesis in the Context of Aging and Diabetes Mellitus
Authors: MANTSOUNGA CHRIS S. , SHARMA SHEILA , LEE CADENCE , CARLEY RACHEL , CHOUDHARY GAURAV , MORRISON ALAN R. 
Published: May 2022

Peripheral artery disease (PAD) caused by atherosclerosis leads to considerable morbidity and mortality throughout the world, in large part, due to tissue damage from both acute and chronic occlusive ischemia. Preclinical studies have identified mechanisms involving bone marrow derived macrophage (BMDM) -dependent angiogenesis in an inflammation suppressed state and we recently defined a novel IL-1beta-dependent transcriptional regulation of the pro-angiogenic isoform of VEGF-A. We sought to understand the impact of diabetes on inflammatory angiogenesis in the context of aging. We hypothesized that the uncoupling of IL-1beta and VEGF-A expression with consequent impairments in angio/arteriogenesis. Control mice at 26-week-old of age or mice with experimental diabetes have reductions of angio/arteriogenesis, using a PAD model of femoral artery ligation that involves macrophage-directed blood flow recovery. Combined aging with chronic diabetes led to further reductions in blood flow recovery consequent to impaired angiogenesis. We also found elevated VEGF-R2 (relative to VEGF-R1) expression in the inflammatory “M1” state which was associated with elevations of IL-1beta and VEGF-A. Interestingly selective inhibition of VEGF-R2 led to reduced VEGF-A expression despite stable IL-1beta levels, suggesting an uncoupling of the relationship between IL-1beta and VEGF-A. Lastly, BMDMs from aged, diabetic mice demonstrated an uncoupling of IL-1beta and VEGF-A expression and VEGF-R2 was decreased in aged, diabetic BMDMs. Defining inflammatory macrophages as key, early drivers of angio/arteriogenesis via IL-1beta and VEGF-A/VEGF-R2 signaling supports a paradigm shift away from inflammation-suppression for adequate healing, allowing for macrophage reprograming strategies that promote appropriate inflammation-dependent healing responses.

Disclosure
C.S.Mantsounga: None. S.Sharma: None. C.Lee: None. R.Carley: None. G.Choudhary: None. A.R.Morrison: None.

Funding
National Institute of Health NIGMS (P20GM103652)
492-P: National Diabetes Prevention Program (DPP) Outcomes during the COVID-Pandemic, Montana, 2020 Compared with 2017–2019
Authors: DUTHIE MARY K. , FERNANDES JESSIE , HOUSE MELISSA , BUTCHER MARCI , HARWELL TODD S. , HELGERSON STEVEN D. , GOHDES DOROTHY M. 
Published: May 2022

In 2020, the COVID-pandemic challenged the delivery of the National DPP and presented unique stressors for participants. Since 2008, Montana’s DPP has maintained a registry to track participant retention, goal achievement, and changes in cardiometabolic (CM) risk. To measure effects of the COVID pandemic on DPP outcomes in Montana, we compared data from participants in 2020 to those in 2017 - 2019. Baseline, 6 and 12-month data were available for 522 participants from 2020 and 2,313 from 2017-2019. Changes in participation and measures of CM were compared using chi-square analysis, t-test and ANOVA analysis. The average number of sessions attended was lower in 2020, 13.6, than in 2017-2019, 14.4 (p=0.02) . The average percent of body weight lost was lower in 2020 at both six-months, 3.9%, and twelve-months, 3.7%, compared to the same measurements in 2017 to 2019, 4.4% (p=0.03) and 4.4% (p=0.01) . Among CM risk measurements, significant differences occurred only for increases in the HDL cholesterol levels measured in 2020, 52.9 mg/dL baseline, 54.7 at 6 months and 56.4 at 12 months, compared to those in 2017 to 2019, 53.6, 52.9 and 55.8 (p=0.00for 6 and p=0.0087 for 12-month) (Table) . During the COVID-pandemic DPP participants continued to lose weight and achieve significant improvements in overall CM risk despite slightly less weight loss compared to participants in previous years.

Disclosure
M.K.Duthie: None. J.Fernandes: None. M.House: None. M.Butcher: None. T.S.Harwell: None. S.D.Helgerson: None. D.M.Gohdes: None.

Funding
Centers for Disease Control and Prevention (NU58DP006517 and NU58DP006610)