bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative analysis of glycated haemoglobin, fasting blood glucose and haematological parameters in Type-2 diabetes patients
Authors: Antwi-Baffour Samuel , Mensah Benjamin Tetteh , Armah Dorinda Naa Okailey , Ali-Mustapha Samira , Annison Lawrence
Published: October 2023

Objective

Diabetes remains a major health problem, and Glycated hemoglobin (HBA1c) and fasting blood glucose (FBG) levels play important roles in its management. Also, chronic hyperglycemia coupled with high HBA1c levels impact inflammation and may alter haematological parameters in diabetes. Hence, the need to assess and correlate HBA1c and FBG levels with selected haematological parameters in patients with type-2 diabetes mellitus as the main objective of this study. The study was cross-sectional involving 384 participants. Five milliliters of blood was collected from each participant and analyzed for HBA1c, FBG levels and full blood count which were correlated statistically.

Results

From the data obtained and analyzed, there were statistically significant correlations between HBA1c and neutrophil count (p < 0.013), plateletcrit (p < 0.036), mean platelet volume (p < 0.019) and platelet distribution width (p < 0.002). There were also significant differences in FBG (p < 0.014), neutrophil count (p < 0.029), red cell distribution width (p < 0.046), mean platelet volume (p < 0.032) and platelet distribution width (p < 0.013) between diabetes patients with HBA1c less than 7.0% and HBA1c more than or equal to 7.0%. The outcome of the study indicates significant correlation of HBA1c with selected haematological parameters. This could make routine haematological parameters a cost-effective means of predicting poor glucose control in diabetes mellitus patients.
Rare case of refractory mixed autoimmune hemolytic anemia in a 6-year-old child: a case report
Authors: Hanna Mirette , Carcao Manuel
Published: October 2023

Background

Mixed autoimmune hemolytic anemia (AIHA) shows combined clinical and laboratory characteristics of warm and cold AIHA. It is relatively uncommon in children. Consequently, knowledge about mixed AIHA prevalence, clinical presentation, treatment options, and prognosis in children is limited to very few case reports.

Case presentation

We describe a six-year-old Asian girl presenting with profound anemia, blood group typing discrepancy and crossmatch incompatibility, post upper respiratory tract infection. Detection of red cell warm and cold reactive autoantibodies, led to the diagnosis of mixed AIHA. Autoantibodies with laboratory evidence of hemolysis persisted despite high dose steroid therapy. Due to the inability to wean further, the patient was subsequently commenced on mycophenolate mofetil to which she seems to be responding.

Conclusions

Mixed AIHA may be notoriously difficult to diagnose and treat. Detailed clinical and laboratory work-up is essential to establish the diagnosis. To the best of our knowledge, this is the first case report of mixed AIHA following upper respiratory tract infection. Awareness of this occurrence is important, as similar to warm AIHA, mixed AIHA should be treated immediately by early initiation of steroid therapy. In addition, prompt supportive care as well as long-term clinical follow-up are required to improve outcomes of these cases.
Adipose-derived, autologous mesenchymal stem cell therapy for patients with post-COVID-19 syndrome: an intermediate-size expanded access program
Authors: Vij Ridhima , Kim Hosu , Park Hyeonggeun , Cheng Thanh , Lotfi Djamchid , Chang Donna
Published: October 2023

Background

Evolving mutations of the novel coronavirus continue to fuel up the pandemic. The virus affects the human respiratory system along with other body systems, causing several sequelae in the survivors of the disease, presented as post-COVID-19 syndrome or long-COVID-19. This protocol utilized Hope Biosciences’ autologous, adipose-derived mesenchymal stem cells (HB-adMSCs) to evaluate safety and efficacy of HB-adMSC therapy to improve signs and symptoms associated with post-COVID-19 syndrome.

Methods

Ten eligible subjects with post-COVID-19 syndrome were enrolled in the program for a duration of 40 weeks who received 5 intravenous infusions of 2 × 108 autologous HB-adMSCs each at week 0, 2, 6, 10 and 14 with a follow-up at week 18 and end of the study at week 40. Safety assessments included incidence of adverse and serious adverse events along with the laboratory measures of hematologic, hepatic, and renal function. Efficacy was examined by quality-of-life assessments, fatigue assessments, Visual analog scale (VAS) of symptoms and monitoring of respiration and oxygen saturation rates.

Results

VAS scores and Fatigue Assessment scores (FAS) showed significant improvements post-treatment (P = 0.0039, ES = 0.91) compared to baseline. Respiration rates and oxygen saturation levels that were within the normal range at the baseline remained unchanged at the end of the study (EOS). Paired comparison between baseline and EOS for short-form-36 health survey questionnaire (SF-36) scores also showed improved quality-of-life with significant improvements in individual SF-36 evaluations. Mostly mild AEs were reported during the study period with no incidence of serious AEs. Also, no detrimental effects in laboratory values were seen.

Conclusions

The results of the expanded access program indicated that treatment with autologous HB-adMSCs resulted in significant improvements in the signs and symptoms associated with post-COVID-19 syndrome as assessed by VAS and FAS scores. Additionally, improvements in the patients’ quality-of-life as demonstrated using SF-36 scores that also showed significant improvements in individual scaled scores. Overall, administration of multiple infusions of autologous HB-adMSCs is safe and efficacious for improvements in the quality-of life of patients with post-COVID-19 syndrome.

Trial registration: Clinical trial registration number: NCT04798066. Registered on March 15, 2021. (https://clinicaltrials.gov/ct2/show/NCT04798066?term=hope+biosciences&cond=Post-COVID-19+Syndrome&draw=2&rank=2).
Inhibitions of monoamine oxidases by ferulic acid hydrazide derivatives: synthesis, biochemistry, and computational evaluation
Authors: Peedikayil Arshida Thottile , Lee Jiseong , Abdelgawad Mohamed A. , Ghoneim Mohammed M. , Shaker Mohamed E. , Selim Samy , Kumar Sunil , Dev Sanal , Kim Hoon , Mathew Bijo
Published: October 2023

Monoamine oxidases (MAOs) regulate neurotransmitters, and changes in their regulation lead to neurogenerative diseases (NDs). Therefore, MAO inhibitors are used to treat NDs. Ferulic acid, a phenolic compound found in various plant species, has been demonstrated to have a variety of biological functions, including anti-inflammatory, anticancer, and neuroprotective effects. In this study, ten ferulic acid hydrazide derivatives (FA1–FA10) were synthesized, and their ability to inhibit monoamine oxidase (MAO) enzymes was tested. Six candidates demonstrated a more pronounced pattern of inhibitory action against MAO-B than against MAO-A. FA3 had the highest inhibitory efficacy in MAO-B inhibition (IC50 value of 1.88 μM), followed by FA9 (2.08 μM). FA3 has a Ki of 1.92 ± 0.73 μM. A reversibility experiment of MAO-B inhibition by FA3 was conducted using dialysis, and the recovery pattern showed FA3 was a reversible MAO-B inhibitor with a similar recovery to safinamide, a reversible reference inhibitor. These results indicate that FA3 is an effective reversible MAO-B inhibitor. In molecular dynamics and docking, FA3 paired with pi-pi stacking helped stabilize the protein ligand in the active site of MAO-B. According to this study, lead compounds can be used as therapeutic agents to treat neurological conditions, such as Parkinson's disease (PD).
How does the correction in lumbar lordosis affect the spinopelvic realignments in degenerative lumbar scoliosis underwent scoliosis surgery?
Authors: Zhang Zifang , Song Jianing , Jia Shu , Tian Zhikang , Zhang Zhenyu , Zheng Guoquan , Meng Chunyang , Li Nianhu
Published: October 2023

Background

To evaluate the effects of correction in lumbar lordosis (LL) that have on full-body realignments in patients with degenerative lumbar scoliosis (DLS) who had undergone long sacroiliac fusion surgery.

Methods

A multi-center retrospective study including 88 DLS patients underwent the surgical procedure of long sacroiliac fusion with instrumentations was performed. Comparisons of radiographic and quality-of-life (QoL) data among that at the pre-operation, the 3rd month and the final follow-up were performed. The correlations between the LL correction and the changes in other spinopelvic parameters were explored using Pearson-correlation linear analysis and linear regression analysis. The correlation coefficient (r) and the adjusted r2 were calculated subsequently.

Results

All radiographic and QoL data improved significantly (P < 0.001) after the surgical treatments. The LL correction correlated (P < 0.001) with the changes in the sacral slope (SS, r = 0.698), pelvic tilt (PT, r = -0.635), sagittal vertical axis (SVA, r = −0.591), T1 pelvic angle (TPA, r = −0.782), and the mismatch of pelvic incidence minus lumbar lordosis (PI–LL, r = −0.936), respectively. Moreover, LL increased by 1° for each of the following spinopelvic parameter changes (P < 0.001): 2.62° for SS (r2 = 0.488), −4.01° for PT (r2 = 0.404), −4.86° for TPA (r2 = 0.612), −2.08° for the PI–LL (r2 = 0.876) and -15.74 mm for SVA (r2 = 0.349). Changes in the thoracic kyphosis (r = 0.259) and pelvic femur angle (r = 0.12) were independent of the LL correction, respectively.

Conclusions

LL correction correlated significantly to the changes in spinopelvic parameters; however, those independent variables including the thoracic spine and hip variables probably be remodeled themselves to maintain the full-body balance in DLS patients underwent the correction surgery.
Custodiol versus blood cardioplegia in pediatric cardiac surgery: a randomized controlled trial
Authors: Elmahrouk Ahmed F. , Shihata Mohammad S. , AL-Radi Osman O. , Arafat Amr A. , Altowaity Musleh , Alshaikh Bayan A. , Galal Mohamed N. , Bogis Abdulbadee A. , Al Omar Haneen Y. , Assiri Wesal J. , Jamjoom Ahmed A.
Published: October 2023

Background

Blood-based cardioplegia is the standard myocardial protection strategy in pediatric cardiac surgery. Custadiol (histidine-tryptophan-ketoglutarate), an alternative, may have some advantages but is potentially less effective at myocardial protection. This study aimed to test whether custadiol is not inferior to blood-based cardioplegia in pediatric cardiac surgery.

Methods

The study was designed as a randomized controlled trial with a blinded outcome assessment. All pediatric patients undergoing cardiac surgery with cardiopulmonary bypass and cardioplegia, including neonates, were eligible. Emergency surgery was excluded. The primary outcome was a composite of death within 30 days, an ICU stay longer than 5 days, or arrhythmia requiring intervention. Secondary endpoints included total hospital stay, inotropic score, cardiac troponin levels, ventricular function, and extended survival postdischarge. The sample size was determined a priori for a noninferiority design with an expected primary outcome of 40% and a clinical significance difference of 20%.

Results

Between January 2018 and January 2021, 226 patients, divided into the Custodiol cardioplegia (CC) group (n = 107) and the blood cardioplegia (BC) group (n = 119), completed the study protocol. There was no difference in the composite endpoint between the CC and BC groups, 65 (60.75%) vs. 71 (59.66%), respectively (P = 0.87). The total length of stay in the hospital was 14 (Q2–Q3: 10–19) days in the CC group vs. 13 (10–21) days in the BC group (P = 0.85). The inotropic score was not significantly different between the CC and BC groups, 5 (2.6–7.45) vs. 5 (2.6–7.5), respectively (P = 0.82). The cardiac troponin level and ventricular function did not differ significantly between the two groups (P = 0.34 and P = 0.85, respectively). The median duration of follow-up was 32.75 (Q2–Q3: 18.73–41.53) months, and there was no difference in survival between the two groups (log-rank P = 0.55).

Conclusions

Custodial cardioplegia is not inferior to blood cardioplegia for myocardial protection in pediatric patients.

Trial registration The trial was registered in Clinicaltrials.gov, and the ClinicalTrials.gov Identifier number is NCT03082716 Date: 17/03/2017
Validation of the hyperbolic temperament questionnaire in Iran
Authors: Komasi Saeid , Chamandoost Zahra , Vaysi Anis , Amirian Mohadese , Rezaeean Hadis , Hopwood Christopher J.
Published: October 2023

Objective

Because of the importance of the cross-cultural study of hyperbolic temperament in increasing knowledge related to borderline personality disorder (BPD), the present study was conducted to test the reliability, construct, criterion, and discriminant validity of the Hyperbolic Temperament Questionnaire (HTQ) in three Iranian samples.

Methods

Using a cross-sectional design, the HTQ 11-item version translated into Farsi was provided to three selected samples (total N = 558, 72% female, 18 to 77 years old with an average of 30.2 and a standard deviation of 10.3). The samples included non-personality disorder samples (n = 194), samples with BPD symptoms (n = 104), and samples with other personality disorder symptoms (n = 260). Data were collected using multiple validating measurements. Factor analysis was used to verify that the HTQ is unidimensional and correlations and regression models were used to examine its associations with other constructs.

Results

Factor analysis confirmed the single-factor structure of the HTQ in two non-personality disorder and BPD samples. The internal consistency of all items and the total scale were acceptable across the samples (α = 0.87 to 0.91). Positive correlations with maladaptive constructs such as negative affectivity and interpersonal sensitivity and negative correlations with adaptive constructs supported the criterion validity of HTQ. The HTQ was specifically related to borderline symptoms, even after controlling for similar constructs such as depression.

Conclusion

The 11-item version of HTQ has acceptable reliability and validity in Iranian samples. Using this short tool for rapid screening of cases with BPD before common procedures such as clinical interviews helps to save diagnostic time and costs.
Diagnosing and monitoring pancreatic cancer through cell-free DNA methylation: progress and prospects
Authors: García-Ortiz María Victoria , Cano-Ramírez Pablo , Toledano-Fonseca Marta , Aranda Enrique , Rodríguez-Ariza Antonio
Published: October 2023

Pancreatic cancer is one of the most challenging cancers due to its high mortality rates. Considering the late diagnosis and the limited survival benefit with current treatment options, it becomes imperative to optimize early detection, prognosis and prediction of treatment response. To address these challenges, significant research efforts have been undertaken in recent years to develop liquid-biopsy-based biomarkers for pancreatic cancer. In particular, an increasing number of studies point to cell-free DNA (cfDNA) methylation analysis as a promising non-invasive approach for the discovery and validation of epigenetic biomarkers with diagnostic or prognostic potential. In this review we provide an update on recent advancements in the field of cfDNA methylation analysis in pancreatic cancer. We discuss the relevance of DNA methylation in the context of pancreatic cancer, recent cfDNA methylation research, its clinical utility, and future directions for integrating cfDNA methylation analysis into routine clinical practice.
Tumor classification of gastrointestinal liver metastases using CT-based radiomics and deep learning
Authors: Tharmaseelan Hishan , Vellala Abhinay K. , Hertel Alexander , Tollens Fabian , Rotkopf Lukas T. , Rink Johann , Woźnicki Piotr , Ayx Isabelle , Bartling Sönke , Nörenberg Dominik , Schoenberg Stefan O. , Froelich Matthias F.
Published: October 2023

Objectives

The goal of this study is to demonstrate the performance of radiomics and CNN-based classifiers in determining the primary origin of gastrointestinal liver metastases for visually indistinguishable lesions.

Methods

In this retrospective, IRB-approved study, 31 pancreatic cancer patients with 861 lesions (median age [IQR]: 65.39 [56.87, 75.08], 48.4% male) and 47 colorectal cancer patients with 435 lesions (median age [IQR]: 65.79 [56.99, 74.62], 63.8% male) were enrolled. A pretrained nnU-Net performed automated segmentation of 1296 liver lesions. Radiomics features for each lesion were extracted using pyradiomics. The performance of several radiomics-based machine-learning classifiers was investigated for the lesions and compared to an image-based deep-learning approach using a DenseNet-121. The performance was evaluated by AUC/ROC analysis.

Results

The radiomics-based K-nearest neighbor classifier showed the best performance on an independent test set with AUC values of 0.87 and an accuracy of 0.67. In comparison, the image-based DenseNet-121-classifier reached an AUC of 0.80 and an accuracy of 0.83.

Conclusions

CT-based radiomics and deep learning can distinguish the etiology of liver metastases from gastrointestinal primary tumors. Compared to deep learning, radiomics based models showed a varying generalizability in distinguishing liver metastases from colorectal cancer and pancreatic adenocarcinoma.
Antifungal bio-coating of endotracheal tube built by overexpressing the
MCP1
gene of
Saccharomyces boulardii
and employing hydrogel as a “house” to antagonize
Candida albicans
Authors: Wei Yunyun , Qiu Jianfeng , Han Ziqiang , Wang Xuanyi , Zhang Hui , Hou Xinya , Lv Xiangwei , Mao Xiaolong
Published: October 2023

Background

For some ICU patients, an artificial airway must be established with an endotracheal tube, but
Candida albicans
can easily adhere to the tube surface and form a biofilm, leading to potentially life threatening fungal infections. Therefore, it is urgent to prevent and reduce
C. albicans
infections introduced by the endotracheal tube. However, there are few antifungal drugs effective against
C. albicans
, and each of these drugs may have adverse effects on human cells.
Saccharomyces boulardii
is regarded as an alternative strategy to inhibit the adhesion of
C. albicans
, but it is affected by environmental stress. We hypothesized that it is feasible to strengthen the antagonistic ability of
S. boulardii
via encapsulating and genetically modification.

Methods

In this study, a bioactive material carrying the overexpressed
MCP1
gene of
Saccharomyces boulardii
was constructed based on one-step photo-crosslinking. This material achieved spatial growth control of
S. boulardii
by encapsulating each
S. boulardii
cell within a hydrogel pore. The bioactive material was coated on an endotracheal tube and tested for its ability to inhibit the adhesion of
C. albicans
. Additionally, the material’s antagonistic activity towards
C. albicans
was evaluated by detecting intracellular Adenosine-triphosphate content, reactive oxygen species level and the activity of antioxidative enzymes. Tissue invasion experiment was executed to further evaluate the anti-adhesion ability of
S. boulardii
bio-coating.

Results

Encapsulating the overexpression of
MCP1
by
S. boulardii
in hydrogel pores enhanced the viability of probiotics in the presence of high salt and oxidation stress. When used as the coating of an endotracheal tube, the
S. boulardii
bioactive material efficiently inhibited the adhesion of
C. albicans
by impairing the activities of superoxide dismutase and catalase and disturbing mitochondrial functions. In vivo, the
S. boulardii
bioactive material coating displayed good biocompatibility and reduced the host tissue invasion and virulence of
C. albicans
.

Conclusions

The integration of genetic modification and immobilization model breaks the bottleneck of previous application of microorganisms, and provides a new way to prevent fungal infections introduced by endotracheal tubes.

Graphical Abstract
Analysis of in vivo humeral rotation of reverse total shoulder arthroplasty patients during shoulder abduction on the scapular plane with a load
Authors: Takahashi Yuji , Nishinaka Naoya , Furuya Kanji , Ikeda Takashi , Jinno Tetsuya , Okawa Atsushi , Sakai Tomoko
Published: October 2023

Background

Few studies have investigated the kinematics after reverse total shoulder arthroplasty (RTSA). This study aimed to compare the shoulder kinematics in RTSA patients during shoulder abduction on the scapular plane with and without a load and yield information regarding the function of stabilizing the joints against gravity for the functional assessment of the shoulder after RTSA, which could lead to changes in postoperative rehabilitation treatment.

Methods

Twenty RTSA patients (7 men, 13 women; mean age: 78.1 [64–90] years) were examined. First, active shoulder abduction in the scapular plane was captured using single-plane fluoroscopic X-ray images. Imaging was performed by stipulating that one shoulder abduction cycle should be completed in 6 s. Two trials were conducted: one under a load equivalent to 2% of body weight and one without a load. Next, a three-dimensional (3D) model of each humeral and scapular component was matched to the silhouette of the fluoroscopic image to estimate the 3D dynamics. By using the 3D dynamic model obtained, the kinematics of the glenosphere and humeral implant were calculated relative to the shoulder abduction angle on the scapular plane and were compared between groups with and without a load. A one-way analysis of variance and a post hoc paired t-test with a statistical significance level of 0.05 were performed.

Results

The humeral internal rotation decreased with a load at shoulder abduction between 40° and 90° on the scapular plane (P < 0.01, effect size: 0.15). No significant differences in scapular upward rotation (P = 0.57, effect size: 0.022), external rotation (P = 0.83, effect size: 0.0083) and posterior tilting (P = 0.74, effect size: 0.013) were observed between groups with and without a load. The main effect was not observed with and without a load (P = 0.86, effect size: 0.0072). However, the scapulohumeral rhythm was significantly greater without a load during shoulder joint abduction between 40° and 60° on the scapular plane.

Conclusion

In RTSA patients, the glenohumeral joint was less internally rotated, and the scapulohumeral rhythm decreased under loaded conditions. It was stabilized against the load through the mechanical advantage of the deltoid muscle and other muscles.
OR07-04 Associations Of Sleep Patterns And Body Mass Index Among African Americans: The Jackson Heart Sleep Study
Authors: Duan Daisy , Jun Jonathan C , Johnson Dayna A , Ahima Rexford S , Bertoni Alain G , Redline Susan , Echouffo Tcheugui Justin B
Published: October 2023

Disclosure: D. Duan: None. J.C. Jun: None. D.A. Johnson: None. R.S. Ahima: None. A.G. Bertoni: None. S. Redline: None. J.B. Echouffo Tcheugui: None.

Background: Obesity and its metabolic complications disproportionately affect African Americans. Sleep may be a modifiable factor that can impact metabolic health. We used objective measures of sleep patterns to assess the relationship between sleep parameters and body mass index (BMI) among African Americans. Methods: The Jackson Heart Study was a prospective cohort study that recruited 5306 African American adults from 3 counties in Jackson, Mississippi, designed to evaluate the etiology of cardiovascular disease among African Americans. We performed a cross-sectional analysis including 913 participants in the Jackson Heart Sleep Ancillary Study (enrolled 2012-2016) who underwent 7-day wrist actigraphy and home sleep apnea tests. We used multivariable linear regression to assess the associations between BMI (outcome; log-transformed for normality) and actigraphy-derived sleep parameters (exposures) that described: sleep timing (sleep onset and mid-sleep time), sleep duration (total sleep duration and night to night variation measured by within-individual standard deviation), and sleep continuity (sleep maintenance efficiency and sleep fragmentation index). Models were adjusted for age, sex, socioeconomic factors, physical activity, smoking, alcohol use, and the presence of moderate to severe obstructive sleep apnea (Apnea Hypopnea Index > 15). Results: Among the included 684 participants with complete data on anthropometric measurements and key covariates (mean age 63 ± 11 years, 66% women, mean BMI 31.8 ± 6.9 kg/m2), average sleep onset was 23:10 ± 1.35 hrs, mid-sleep time was 2:55 ± 1.20 hrs, total sleep duration was 6.7 ± 1.15 hrs, median night-to-night variation was 1.2 hrs (IQR 0.8-1.5), median sleep maintenance efficiency was 88.9% (IQR 85.7-91.5), and median sleep fragmentation index was 28.4% (IQR 23.3-34). In adjusted models, sleep onset (β 0.013, p=0.02) and mid-sleep time (β 0.012, p=0.047) were positively associated with log transformed BMI, while sleep maintenance efficiency was negatively associated with log transformed BMI (β −0.004, p=0.009). Total sleep duration, night to night sleep duration variability, and average sleep fragmentation index were not associated with BMI in adjusted models. Conclusions: Later sleep timing and poor sleep continuity were associated with higher BMI among African Americans in the Jackson Heart Sleep Study. Our findings suggest the importance of circadian influence and sleep disruption as factors that influence metabolic health.

Presentation: Thursday, June 15, 2023
OR10-03 Murine Bimagrumab Co-administration With Incretin Agonists Results In Additive Efficacy And Superior Quality Weight Loss In The Mouse Diet-induced Obesity Model
Authors: Nguyen Kevin , Wang Xingjuan , Xu Deming , Klickstein Lloyd B
Published: October 2023

Disclosure: K. Nguyen: Employee; Self; Versanis Bio. X. Wang: None. D. Xu: None. L.B. Klickstein: Employee; Self; Versanis Bio. Stock Owner; Self; Novartis Pharmaceuticals.

Bimagrumab is an activin type II receptor (ActRII) antagonist currently in phase 2b clinical development for the treatment of obesity and other cardiometabolic diseases. In overweight and obese patients with T2DM, bimagrumab caused >20% body fat loss over 48 weeks of therapy while concomitantly producing a 4% increase in muscle mass; the net effect is higher quality weight loss than that achieved by dieting or incretin agonists, with weight loss quality defined as the percentage of weight loss represented by fat mass loss. Because the mechanisms of action and target organs for bimagrumab and incretin agonists are largely non-overlapping, we designed mouse experiments to investigate whether adding bimagrumab to incretin therapy might be additive with respect to fat mass loss and improve the quality of weight loss by attenuating the lean mass loss that accompanies incretin treatment. C57Bl/6J mice at 5-6 weeks of age were fed a 60% fat diet for 25 weeks and reached an average body weight of 54 grams at the start of drug therapy. Each group of mice (n=8) received a murinized version of bimagrumab, CDD866, 20 mg/kg i.p. weekly and/or semaglutide 40 µg/kg s.c. daily, tirzepatide at 45 µg/kg s.c. daily, or liraglutide at 20 µg/kg s.c. twice daily. The high fat diet was continued through the 3-week treatment period. Food intake and body weight were monitored twice weekly, while clinical observations, body composition by MRI and physical activity were assessed once weekly. At the doses and schedules above, the rank order of efficacy with the three incretin agonists tested, as assessed by change in body weight over 3 weeks, was tirzepatide (-13.7g) > semaglutide (-8.6g) > liraglutide (-4.0g), the same order of efficacy as is observed in humans. Adding CDD866 20 mg/kg i.p. weekly to each of tirzepatide, semaglutide or liraglutide therapy increased weight loss to -14.5g, -9.8g and -4.5 g, respectively. The weight loss quality (100 x calculated fat mass loss in grams divided by total body weight loss in grams), was 74.7%, 58.8% and 42.5% for tirzepatide, semaglutide and liraglutide, respectively, and in combination with CDD866 weight loss quality improved to 96.4%, 104.6% and 122.8%, respectively. Fat mass loss > 100% of total weight loss reflects both the additive fat mass loss and the muscle mass gain due to CDD866. A phase 2b clinical study of bimagrumab +/- semaglutide is ongoing to learn if these favorable results will translate to humans (NCT05616013).

Presentation: Friday, June 16, 2023
FRI013 Free Fatty Acid Receptors 2 And 3 Mediate The Beneficial Effects Of Fiber
Authors: Pandya Nupur S , Priyadarshini Medha , Layden Brian T
Published: October 2023

Disclosure: N.S. Pandya: None. M. Priyadarshini: None. B.T. Layden: None.

The Gut Microbiome (GM) is a key player in whole body metabolism. Microbial dysregulation and dysbiosis have been linked to multiple pathologies including obesity and type 2 diabetes. Microbes influence host function by releasing various metabolites when interacting with ingested materials. Key metabolites include short chain fatty acids (SCFAs) produced through microbial fermentation of fiber. Fiber intake is known to increase GM diversity; this process has been suggested to protect against obesity and type 2 diabetes. While SCFAs have been implicated in this process, the overall mechanism is still unclear. Free fatty acid receptors 2 and 3 (FFA2 and FFA3) occupy a unique position through which the GM can exert an effect on host metabolism. These G-protein coupled receptors are known to sense SCFAs and can modulate the subsequent secretion of incretin and insulin hormones thus regulating host appetite and blood-glucose control. FFA2 and FFA3 are expressed in many tissues, including adipocytes, neurons, and most importantly, intestinal enteroendocrine L cells and pancreatic β cells. For this reason, complete understanding of their function is necessary, and elucidating their signaling mechanisms may have significant therapeutic value in the treatment of the obesity epidemic and diabetes. Here, we seek to understand the whole-body impact of the gut microbiota-SCFA-FFA2/3 axis in the metabolically protective role of fiber. We used here a novel whole-body FFA2/FFA3 double knockout (F2,3-dKO) mouse model to obtain a holistic understanding of SCFA sensing mechanisms when mice are fed obesogenic diets supplemented with or without fermentable fiber. Double knockout mice, alongside matched wild-type controls were challenged with either a high fat western diet (WD), or WD supplemented with 20% fructooligosaccharides (FOS), a fermentable fiber (WD + 20% FOS). Preliminary data showed a significant rise in body weight, fat mass, and insulin resistance in WD fed F2,3-dKO mice alongside matched wild-type controls. Wild-type mice, when challenged with WD supplemented with fiber, were protected from this effect with only a mild increase in body weight and insulin resistance. Interestingly, F2,3-dKO mice, fed WD + 20% FOS were insensitive to fiber induced metabolic benefits. This suggests that FFA2 and FFA3 are essential for fermentable fiber mediated metabolic benefits against WD induced obesity. Further studies are now aimed to understand the mechanism behind this protective effect.

Presentation: Friday, June 16, 2023
FRI019 Mono(ADP-Ribosyl)ation Of Ribosomal Proteins During Adipogenesis
Authors: Tan Xinrui , Challa Sridevi , Stokes MiKayla S , Nandu Tulip Sunil , Lee Kraus W
Published: October 2023

Disclosure: X. Tan: None. M.S. Stokes: None. T.S. Nandu: None. W.L. Kraus: None.

ADP-ribosylation is a post-translational modification of proteins in which ADP-ribose units from NAD+ are covalently linked to various amino acids on substrates by ADP-ribosyltransferase (ART) enzymes. The NAD+ required for these reactions is synthesized by nicotinamide mononucleotide adenylyl transferases (NMNATs), which serve as the key NAD+ synthase enzymes in the salvage pathway. The three cellular NMNATs have different subcellular localizations (NMNAT-1 in the nucleus, NMNAT-2 in the cytoplasm, and NMNAT-3 in the mitochondria). We have shown previously that NMNAT-2 protein is rapidly and robustly induced during adipogenesis through a stabilization mechanism, causing rapid reduction in nuclear nicotinamide mononucleotide (NMN) levels and decreased PARP1 catalytic activity, leading to an increased expression of proadipogenic genes. We also recently demonstrated that NMNAT-2 support the catalytic activity of PARP16, an endoplasmic reticulum-localized enzyme, to maintain protein homeostasis in ovarian cancer cells by mono(ADP-ribosyl)ation (MARylation) of ribosomal proteins. The biological functions of increased cytoplasmic NAD+ synthesis by NMNAT-2 in adipocytes, however, is unknown. Our results demonstrate a reciprocal decrease of nuclear poly(ADP-ribose) (PAR) levels and increase of cytosolic MAR levels during the differentiation of 3T3-L1 preadipocytes, which is driven by the induction of NMNAT-2. The increase in cytosolic MAR levels leads to enhanced ribosome MARylation, and knockdown of NMNAT-2 or PARP16 results in reduced ribosome MARylation. Analysis of ribosomes isolated from differentiated 3T3-L1 cells revealed the enrichment of MARylation in fractions containing monosomes. Using TMT mass spectrometry, we identified numerous high confidence of ADP-ribosylation sites on ribosome proteins in both undifferentiated and differentiated 3T3-L1 cells, with over 30 sites showing significant increases in differentiated adipocytes. We are now examining the relationship between the MARylation of ribosome proteins and translational programming during adipogenesis to expand our understanding of MARylation in physiology and disease.

Presentation: Friday, June 16, 2023
FRI026 PPARγ Antagonists Induce Aromatase Transcription In Human Adipose Tissue Cells
Authors: Ardenkjær-Skinnerup Jacob , Petersen Patricia S S , Hadrup Niels , Ravn-Haren Gitte , Emanuelli Brice , Vogel Ulla B , Brown Kristy A
Published: October 2023

Disclosure: J. Ardenkjær-Skinnerup: None. P.S. Petersen: None. N. Hadrup: None. G. Ravn-Haren: None. B. Emanuelli: None. U.B. Vogel: None. K.A. Brown: None.

Peroxisome proliferator-activated receptor gamma (PPARγ) activation in adipose stromal cells (ASCs; adipocyte precursors) is associated with decreased expression of the estrogen biosynthetic enzyme, aromatase, encoded by the CYP19A1 gene. A number of chemicals and endocrine disruptors can affect PPARγ function. For example, ethanol-mediated inhibition of PPARγ activity is associated with increased risk of breast cancer,1 and a potential mechanism has been suggested to involve upregulation of aromatase. It is therefore hypothesized that inhibitors of PPARγ will induce aromatase expression and may act as breast carcinogens. This study aimed to explore the effect of PPARγ antagonists on the expression of aromatase in cells from human adipose tissue. Human adipose tissue was obtained from abdominoplasty or reduction mammoplasty surgeries. Explants, adipocytes and ASCs were collected for culture and/or gene expression analysis. Primary ASCs and the hTERT A41 hWAT ASC line were differentiated in the presence of PPARγ antagonists followed by gene expression analysis or lipid staining. Adipose tissue explants and A41 cells were treated for 24 or 48 h with PPARγ agonist or antagonist, and gene expression analysis was performed. Finally, PPARγ was overexpressed in A41 cells and/or treated with a PPARγ agonist to study the effect of PPARγ protein level and activation on aromatase expression. Aromatase expression was higher in human ASCs than in mature adipocytes. Exposure of ASCs to PPARγ antagonists during differentiation inhibited lipid accumulation and resulted in higher expression of aromatase. PPARγ overexpression and agonist treatment repressed aromatase expression in A41 cells, while antagonist treatment in differentiated A41 cells resulted in increased aromatase expression. A similar tendency was observed in adipose tissue explants. In conclusion, the results suggest that PPARγ regulates aromatase through two separate mechanisms. Exposure of human ASCs to PPARγ antagonists indirectly upregulates aromatase expression by inhibition of adipogenesis. In addition, PPARγ regulates aromatase in differentiated ASCs via a more acute mechanism, not related to adipocyte differentiation.

1. Petersen RK, Larsen SB, Jensen DM, et al. PPARgamma-PGC-1alpha activity is determinant of alcohol related breast cancer. Cancer Lett. 2012;315(1):59-68.

Presentation: Friday, June 16, 2023
FRI033 Metabolically Healthy Obesity In A Young Population Assisted By The Family Health Strategy
Authors: Boghossian Rodney Barbera , Ferreira Maselli Giovanna Francesca , Lopes Carolina Campello , de Vasconcellos Clara Avelar Mendes , Parente Carlos Augusto , Santos Ferreira Deisianny Dos , Garcia Juliana Câmara , Senra Guimarães Luana Moreira , Muxfeldt Elizabeth Silaid , Damião Charbel Pereira
Published: October 2023

Disclosure: R.B. Boghossian: None. G.F. Maselli: None. C.C. Lopes: None. C.A. Vasconcellos: None. C.A. Parente: None. D.D. Ferreira: None. J.C. Garcia: None. L.M. Guimarães: None. E.S. Muxfeldt: None. C.P. Damião: None.

Background: Obesity is increasing in younger populations, and is associated with a high cardiovascular (CV) risk, however, it is not clear whether metabolically healthy obesity (MHO) may have a lower CV risk or if it is just an earlier stage of the disease. Objective: To evaluate the prevalence and cardiovascular (CV) risk factors associated with metabolically healthy obesity (MHO) in a young population assisted by a Family Health Care unit in a large urban center. Design and Methods: A cross-sectional population study for CV risk assessment in adults aged 20-50 years old from a Family Health Care unit. Demographic, anthropometric data and CV risk factors were recorded. All underwent office blood pressure (BP) measurements, laboratory evaluation (lipid and glycidic profile), Home Blood Pressure Monitoring (HBPM), and bioimpedance. Obesity was defined as a body mass index (BMI) > 30 kg/m2 and MHO are those who have less than 3 of the following criteria for metabolic syndrome: office BP higher or equal to 130 x 85 mmHg, hypertension, fasting blood sugar higher or equal to 100 mg/dL, HDL < 40 mg/dL (men) and 50 mg/dL (women), triglycerides >150 mg/dL and waist circumference > 102 cm (men) and > 88 cm (women). Results: A total of 726 individuals were evaluated (60% female; mean age 37 ± 9 years). The prevalence of obesity was 24.9%, of which 73.4% were classified as MHO. Obeses are older, with a higher prevalence of physical inactivity (51% vs 42%, p=0.03), hypertension (44% vs 19%, p<0.001), and diabetes (10% vs 2%, p=0.001) with higher office and home blood pressure. MHO compared to unhealthy ones are significantly younger and smoke less. Despite being obese, they have lower waist circumference (102 vs 110 cm, p=0.03), with lower office and home BP. There is no significant difference in relation to corporal composition. Conclusion: MHO was more prevalent in this young population and seems to have a lower CV risk, however it is not clear whether these younger and less obese individuals are only at an earlier stage of the disease. Perhaps the CV diseases onset is postponed for a few years. Even so, these individuals should not be excluded from public health policies as a form of primary prevention

Presentation: Friday, June 16, 2023
FRI034 Visceral Adiposity Index Is Associated With Cardiovascular Diseases, Independent Of Body Mass Index: Analysis From NHANES Study
Authors: Ayesh Hazem , Bradley Anna Barton
Published: October 2023

Disclosure: H. Ayesh: None. A.B. Bradley: None.

Introduction: Cardiovascular diseases (CVD) are associated with significant mortality and morbidity. Early identification of at-risk individuals plays an essential role in the treatment and management of CVD. There are multiple reports in the literature that Visceral Adiposity Index (VAI), has been associated with CVD. In this study, we will investigate the association of VAI with CVD, independent of body mass index (BMI), age, and diabetes status. Methods: A sample of 6587 individuals were selected from the NHANES study population (2011-2020). The sample included all individuals in the NHANES population (2011-2020) who are above 18 years and have waist circumference (WC), serum high-density lipoprotein (HDL) level, and serum triglyceride level (TG) available to calculate VAI. CVD status was assigned based on the question “Ever told you had coronary heart disease” from the NHANES survey. VAI for men was calculated using the formula “(WC/(39,68+(1.88*BMI) *(TG/1.03) *(1.31/HDL)”. VAI for women was calculated using the formula “(WC/(36,58+(BMI *1.89) *(TG/0.81) *(1.52/ HDL)” .VAI values were divided into 4 quartiles as follows: 1st(<1.81), 2nd (< 3.03), 3rd(< 5.09), 4th(> 5.09). Logistic regression analysis was performed to study the association between VAI and CVD. Statistical analysis was adjusted for age, BMI, and diabetes status. Results: Statistical analysis showed a statistically significant association between CVD and VAI independent of age, BMI and diabetes status. The odds of CVD were higher in the VAI 4th quartile group compared to the 1st quartile group with an odds ratio of 1.44 (95% CI 1.05-1.98), P value 0.02. Discussion/Conclusion: These results indicate that VAI can serve as a screening tool to identify individuals at risk for cardiovascular diseases. Waist circumference measurements, serum triglyceride levels, and high-density lipoproteins serum levels values are often easily accessible in clinical practice. Implementation of auto-calculation of VAI in electronic health records will provide robust screening and monitoring tools to identify individuals at risk for CVD, especially those with normal BMI. Future high-quality prospective studies will be helpful to further understand the association.

Presentation: Friday, June 16, 2023
FRI035 Comparative Study Of The Changes In Body Composition According To Age And The Associations With The Risk Of Diabetes Mellitus By Races
Authors: Jang Seol A , Kim Kyoung Min , Kim Chul Sik , Park Seok Won
Published: October 2023

Disclosure: S. Jang: None. K. Kim: None. C. Kim: None. S. Park: None.

Introduction: The changes in body composition with aging are known to be associated with the risk of various chronic diseases. But the body composition changes with age among different races, is not well studied. This study aimed to investigate the racial differences in the changes of body composition according to age and the association with prevalent diabetes mellitus. Methods: A total of 37,153 participants was include in the study. 27,864 Korean from the Korea National Health and Nutrition Examination Surveys (KNHANES) 2008-2011 and 9,289 from the National Health and Nutrition Examination Survey (NHANES) 2003-2006 whose age ranged from 20 to 85 years were analyzed. Body composition was measured by dual-energy X-ray absorptiometry (Hologic Horizon) in both cohorts. Relative body composition measures based on young adult (20-29 years) were compared. The association of body composition measures and diabetes were analyzed. Results: Compare to other three races from NHANES, Korean men and women had a lower BMI. Total percentage fat tended to increase with age in all races, but degree of increase with age was not higher in Korean men than in other races and a similar trend was observed in Korean women. Regarding the changes in lean mass, men and women showed different patterns. In men, non-Hispanic white showed peak levels in their 40s and then tended to decrease. All other races showed peaks in their 20s and 30s, and subsequently decreased. Compared to other races, the decline according to age was the largest in Korean men. For women, in all races, the pattern was maintained even after their 20s until their 40s or 50s, and then decreased. The degree of decline was similar in all races. In men, higher fat percentage and lower lean mass were associated with prevalent diabetes in all races. In women, however, higher fat percentage and lower lean mass were associated with prevalent diabetes in only Korean and non-Hispanic white. Conclusion: The changes in body composition according to age vary by race and its association with prevalent diabetes also differs. The clinical significance of changes in body composition according to age and race in chronic diseases needs to be further clarified.

Presentation: Friday, June 16, 2023
FRI050 A Cross-sectional Study Of Parental Outdoor Play Preferences And Association With Child Overweight And Obesity
Authors: Gavryutina Irina , Bochner Risa , Chin Vivian , Bargman Renee
Published: October 2023

Disclosure: I. Gavryutina: None. R. Bochner: None. V. Chin: None. R. Bargman: None.

Background: Childhood obesity is highly prevalent among certain populations of New York City (NYC). Objectives: This cross-sectional study examined the associations between parental attitudes about outdoor activities and playground utilization on child overweight and obesity. Methods: A questionnaire was developed and distributed among parents of 1-13 aged children at ambulatory pediatric clinics in Brooklyn, New York. Parents were asked about time spent outdoors and factors, that can affect it, such as outdoor temperature, winter season, precipitation, concerns about overall safety and COVID-19. Anthropometric data was collected on children and demographic data on both children and parents. Children were divided into 2 groups - those above and below 85% of BMI and associations between parental outdoor play preferences and beliefs with pediatric overweight and obesity were studied. Unadjusted and adjusted relationships between outdoor play preferences and child with BMI ≥85% were analyzed. Results: Of 104 children included in the study 57 were of normal weight and 47 were overweight or obese. The parents of children in both groups were mostly immigrants. There was no statistically significant difference in child age, sex, race, ethnicity and birth country between children with BMI <85% and with BMI ≥85% (P > 0.05, NS). Most parents of children with BMI <85% reported frequent playground utilization, considered longer hours to spend outside on weekdays, reported a larger total temperature range for outdoor playground utilization and a lower tolerable minimum temperature compared to parents of children with BMI ≥85%, p<0.05. Only having a parent born outside of the US remained a significant predictor of overweight and obesity in the final model. Conclusions: Parents of children with BMI<85% are more willing to spend time outdoors, regardless of weather, tolerate wider temperature ranges and lower temperature minimums, have less concern about wet weather and their children are housebound for shorter periods. Immigrant parents are protective against overweight. Concern must be paid to factors that affect outdoor activity in cold climates and mitigation strategies developed to improve children’s health.

Presentation: Friday, June 16, 2023