bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of serum survivin as a predictor of response to biological treatment in rheumatoid arthritis patients
Authors: Salama Sherihan M. , Fawaz Shereen I. 
Published: October 2023

Abstract
Background
Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disorder characterised by synovial hypertrophy, proliferation, and pannus formation encroaching on articular structures resulting in uncontrolled spread of joint destruction. Survivin is an anti-apoptotic protein that plays an important role in tissue growth and tumour development. The objective of this research is to study the role of Survivin as a predictor of treatment response to anti-tumor necrosis factor (anti-TNF) in RA patients who had failure of conventional disease modifying anti rheumatic drugs (DMARDs) treatment.

Results
All patients had active RA evaluated with DAS 28 activity score: 73.3% of them had high disease activity, while 22.7% were in moderate activity. Serum survivin level ranged from 725 pg/ml to 2750 pg/ml. Its level was significantly higher in patients than in controls with a p value of < 0.001. After receiving anti-TNF treatment for 3 months, serum survivin level was reassessed, and it ranged from 525 pg/ml to 2100 pg/ml. There was a significant decreased in the biomarker serum level after receiving the treatment when compared to its level before starting treatment.

Conclusion
Our results showed that the assessment of serum survivin may be a useful diagnostic tool for detection of RA patients also it has a valuable predictive value in assessment of responce to biologic treatments given to the patients. This conclusion was reached after detection of high survivin levels in the sera of RA with high disease activity and reduced functional outcomes. Moreover, the biomarker has a good prognostic value in detection of response to biologic treatment indicated by the reduction of serum level after receiving the treatment and improvement of clinical disease activity.
Comparing tuberculosis symptom screening to chest X-ray with artificial intelligence in an active case finding campaign in Northeast Nigeria
Authors: John Stephen , Abdulkarim Suraj , Usman Salisu , Rahman Md. Toufiq , Creswell Jacob 
Published: October 2023

Abstract
Background
Ultra-portable X-ray devices with artificial intelligence (AI) are increasingly used to screen for tuberculosis (TB). Few studies have documented their performance. We aimed to evaluate the performance of chest X-ray (CXR) and symptom screening for active case finding of TB among remote populations using ultra-portable X-ray and AI.

Methods
We organized screening camps in rural northeast Nigeria, and all consenting individuals ≥ 15 years were screened for TB symptoms (cough, fever, night sweats, and weight loss) and received a CXR. We used a MinXray Impact system interpreted by AI (qXR V3), which is a wireless setup and can be run without electricity. We collected sputum samples from individuals with an qXR abnormality score of 0.30 or higher or if they reported any TB symptoms. Samples were tested with Xpert MTB/RIF. We documented the TB screening cascade and evaluated the performance of screening with different combinations of symptoms and CXR interpreted by AI.

Results
We screened 5297 individuals during 66 camps: 2684 (51%) were females, and 2613 (49%) were males. Using ≥ 2 weeks of cough to define presumptive TB, 1056 people (20%) would be identified. If a cough of any duration was used, the number with presumptive TB increased to 1889 (36%) and to 3083 (58%) if any of the four symptoms were used. Overall, 769 (14.5%) had abnormality scores of 0.3 or higher, and 447 (8.4%) had a score of 0.5 or higher. We collected 1021 samples for Xpert testing and detected 85 (8%) individuals with TB. Screening for prolonged cough only identified 40% of people with TB. Any symptom detected 90.6% of people with TB, but specificity was 11.4%. Using an AI abnormality score of 0.50 identified 89.4% of people with TB with a specificity of 62.8%.

Conclusions
Ultra-portable CXR can be used to provide more efficient TB screening in hard-to-reach areas. Symptom screening missed large proportions of people with bacteriologically confirmed TB. Employing AI to read CXR can improve triaging when human readers are unavailable and can save expensive diagnostic testing costs.
FRI011 Exploring The Contribution Of PARP1-mediated Site-specific ADP-Ribosylation Of C/EBPb In Macrophages To Diet-induced Obesity
Authors: Whitaker Amy L , Gupte Rebecca , Nandu Tulip Sunil , Lee Kraus W 
Published: October 2023

Abstract
Disclosure: A.L. Whitaker: None. R. Gupte: None. T.S. Nandu: None.
Inflammation is an important component of the pathological effects of obesity, which are mediated in part by adipose-associated macrophages (TAMs). Signal-regulated post-translational modifications in the TAMs help modulate the transcriptional programs that mediate biological outcomes. ADP-ribosylation is a posttranslational modification that regulates various cellular processes, including macrophage activation. ADP-ribosylation is the covalent attachment of ADP-ribose units on proteins by poly(ADP-ribose) polymerase (PARP) enzymes, mainly PARP1 in the nucleus. We have shown that ADP-ribosylation of key transcription factors (e.g., C/EBPβ and STAT1α) by PARP1 regulates adipogenesis, as well as pro-inflammatory responses in macrophages. Here we aim to investigate the role of PARP1-mediated ADP-ribosylation of C/EBPβ in inflammation and obesity using monocyte-specific mouse models. We have found that knockout (KO) of PARP1 in the monocyte/macrophage lineage (i.e., using a LysM-Cre driver) results in dramatic weight gain in mice with a nearly 2-fold increase in fat body mass in animals fed a high fat diet. Further analysis revealed decreases in adipose-associated macrophages and adipose hypertrophy, as well as increased hepatic lipid accumulation. Our findings exemplify the critical role that PARP1 in macrophages plays in maintaining homeostasis in key metabolic tissues. Moreover, our results indicate that regulation by PARP1 in macrophages contributes to resistance of diet-induced obesity through tissue-collaborative mechanisms. Our ongoing experiments suggest that PARP1 regulates LPS-induced inflammatory gene expression in macrophages. PARP1 controls LPS-mediated gene expression, in part, by ADP-ribosylating two sites (Glu 135 and Glu 139) in the regulatory domain of C/EBPβ; mutation of these sites inhibits PARP1-mediated PARylation of C/EBPβ and LPS-mediated gene expression through C/EBPβ. Additionally, treatment with a PARP inhibitor decreases LPS-mediated gene expression associated with upstream C/EBPβ enhancers. Moreover, treatment with a PARP inhibitor also decreases histone H3 lysine 27 acetylation (H3K27ac) at these C/EBPβ enhancers.
To investigate the physiological impact of loss of C/EBPβ ADP-ribosylation in macrophages, we have generated a knock-in mouse model for inducible monocyte-specific expression of a C/EBPβ ADP-ribosylation site mutant (CebpbE135A/E139A). This is the first physiological model for the study of site-specific ADP-ribosylation in vivo. Using this model, we are investigating the impact of site-specific ADP-ribosylation of C/EBPβ in mice fed a high fat diet. With these studies, we hope to reveal the specific roles of PARP1-mediated ADP-ribosylation in diet-induced obesity.
Presentation: Friday, June 16, 2023
FRI039 Endothelial Dysfunction Is Associated With Adiponectin And Leptin In Adolescents With PCOS
Authors: Gavryutina Irina , Badran Ahmed , Thakkar Amruta , Bargman Renee , Umpaichitra Vatcharapan , Chin Vivian 
Published: October 2023

Abstract
Disclosure: I. Gavryutina: None. A. Badran: None. A. Thakkar: None. R. Bargman: None. V. Umpaichitra: None. V. Chin: None.
Endothelial dysfunction (ED) was found to be prevalent in women with polycystic ovarian syndrome (PCOS) and was associated with increased leptin and decreased adiponectin levels but has not been studied in children. We performed a cross-sectional study of non-smoking adolescents aged 12-19 years old with PCOS by NIH-criteria (n=20) and controls (n=7) to study the differences in ghrelin, endothelin, anti-mullerian hormone (AMH), leptin, adiponectin and reactive-hyperemia index (RHI) a non-invasive single measure of ED using EndoPAT®. Exclusion criteria were: pregnancy, diabetes, thyroid disease, adrenal disorder, hepatic, cardiovascular disease, hypertension, or medications (other than metformin or oral contraceptive pills which were allowed for the PCOS group). Between PCOS and control groups, there was no difference (mean±SD) in age (16.5±1.8 vs 17.1±2.3 years, p=0.31), BMI (35.7 ±9.7 vs 30.9±10.3 kg/m2, p=0.15) and A1C levels (5.45±0.4 vs 5.37±0.15%, p=0.22). Total and free testosterone was higher in PCOS group (60.7±21.8 vs 34.6±12.8 ng/dl, p=0.00063; 8.51 vs 3.76, p=0.0019, respectively). PCOS group had worse (lower) RHI (1.26±0.43 vs 1.72±0.40, p=0.015, normal RHI &gt;1.67). PCOS group had higher leptin (1085.5±116.9 vs 896.4±176 pg/ml, p=0.014) and lower adiponectin (2.02±0.19 vs 2.27±0.13 µg/ml, p=0.001). There were no differences in endothelin-1 (10.9±1.2 vs 34.3±3.1 pg/ml, p=0.11), ghrelin (6060.1±13057.2 vs 5495.7±5474 pg/dl, p=0.44) and AMH levels (11.86±27 vs 3.8±10.1, p=0.14). HOMA-IR or insulin resistance was not significantly different between the PCOS and control groups (2.05 vs 3.48, p=0.26). Leptin is a proinflammatory product of adipose tissue and via its receptor on the endothelium, likely promotes platelet aggregation, thrombosis and stimulation of free radical production contributing to ED. Adiponectin on the other hand, is known to reduce levels of TNFα and suppress its inflammatory effects on endothelial cells. Low adiponectin has previously been found in women with PCOS when corrected for BMI and even insulin resistance. Our adolescents with PCOS had lower RHI, higher leptin and lower adiponectin levels. These findings suggest increased risk of cardiovascular disease in adolescents which has not been previously reported in children before. Further studies are needed to investigate the relationship between ED and differences in leptin and adiponectin in adolescents with PCOS.
Presentation: Friday, June 16, 2023
FRI081 Quality Improvement Initiative To Improve Management Of Obesity In A Primary Care Resident Continuity Clinic
Authors: Fernandez Maria Gabriela , Hillhouse Melodie , Ozimek David , Salvo Marissa 
Published: October 2023

Abstract
Disclosure: M.G. Fernandez: None. M. Hillhouse: None. D. Ozimek: None. M. Salvo: None.
Background: Obesity is a leading health concern in the US and a growing epidemic worldwide. Despite the substantial evidence on weight management interventions, it remains the least commonly addressed medical problem. Physicians also document obesity infrequently in medical records. It has been well established that increasing documentation of obesity improves its management as a chronic disease. Objective: The main aim of our project was to increase the percentage of patients with a body mass index (BMI) ≥30kg/m2 with documented obesity in the electronic medical record (EMR) from 42% to 70%. The second aim was to increase the percentage of patients with a BMI ≥30kg/m2 prescribed weight loss pharmacotherapy from 10% to 40%. The project was performed in an Internal Medicine residency program continuity clinic over six months. Methods: We used three cycles of the Plan-Do- Study-Act methodology; all included education in obesity medicine, distribution of a hard copy list of the patients who met inclusion criteria, and EMR message reminders to address obesity by the following medical appointment. The EMR was used to generate reports to track outcomes. The first report listed all the resident clinic patients with a documented BMI ≥30kg/m2. The following list the number of patients with BMI ≥30kg/m2 and a corresponding diagnosis of obesity in their chart. The last report listed the number of patients with BMI ≥30kg/m2 on weight loss pharmacotherapy. Reports were generated bi-monthly, and percentages were used to determine the efficacy of each cycle. Results: There were 25% of residents’ patients who met project inclusion criteria. Of this, 11% were prescribed pharmacotherapy at baseline. Of those receiving treatment, 98% had type 2 diabetes. After the interventions, the documentation of obesity in the EMR increased from 42% to 60%. As a result, the overall number of patients on weight loss pharmacotherapy increased from 10.53% to 12.68%. Conclusion: The overall goal of the interventions was successful. There was an increase in both EMR documentation of obesity and increased weight loss pharmacotherapy prescribing; however, both were lower than anticipated. It was also found that the resident physicians responded more to printed metrics of their population of patients. In addition, physicians were more susceptible to treating patients when obesity was documented as a chronic disease. However, this project emphasizes that more efforts should be made to engage residents in multidisciplinary training to improve the management of obesity and increase tools to navigate through barriers to obesity treatments.
Presentation: Friday, June 16, 2023
SAT652 The Expression Of The Immunoproteasome Subunit Psmb9 Is Related To Obesity And The Differentiation Of Human Preadipocytes
Authors: Cui Yan , Zhang Xiaoxiao , You Lianghui , Zhong Hong , Cui Xianwei , Ji Chenbo 
Published: October 2023

Abstract
Disclosure: Y. Cui: None. X. Zhang: None. L. You: None. H. Zhong: None. X. Cui: None. C. Ji: None.
Obesity and its associated chronic diseases, such as type 2 diabetes mellitus, hypertension, and coronary artery disease, afflicting adults and children globally. PSMB9, a proteolytic subunit of the immunoproteasome that shapes the repertoire of antigenic peptides, is hypothesized to be associated with obesity. To investigate this association, we examined PSMB9 expression in primary mature adipocytes from obese and normal individuals. LC-MS/MS-PRM was used to quantify PSMB9 content in primary mature adipocytes, revealing a negative correlation between PSMB9 content and obesity while positively correlated with high-density lipoprotein levels. Furthermore, we examined the effect of PSMB9 on human preadipocyte differentiation. During the early stages of differentiation, the expression of PSMB9 was at its highest level, decreasing as preadipocytes matured. Overexpression of PSMB9 significantly inhibited preadipocyte differentiation, resulting in reduced lipid droplets and decreased expression levels of classical differentiation markers such as FABP4, C/EBPα, and PPARγ. These findings suggest that PSMB9 could be a potential therapeutic target for preventing and treating obesity and metabolic disorders. In conclusion, our study provides insights into the role of the immunoproteasome in obesity and highlights the importance of further exploration of this pathway.
Presentation: Saturday, June 17, 2023
SAT156 Two Cases Of Hypoglycemia From Inhalation Of Heroin Adulterated With A Sulfonylurea
Authors: Kim Keun Young , Hwang Jessica , Sam Susan 
Published: October 2023

Abstract
Disclosure: K. Kim: None. J. Hwang: None. S. Sam: None.
Context: Hypoglycemic disorders in non-diabetic patients are rare. In the setting of concomitant illicit opioid abuse, hypoglycemia is highly unusual and an underlying cause should be systematically investigated. Objective: We report two separate cases of non-diabetic women both admitted to our intensive care unit for critical hypoglycemia secondary to inhaled heroin containing sulfonylureas. Case 1—A 51 year old female with a history of heroin addiction (on methadone) was brought to the emergency department with altered mental status. She was found to have refractory hypoglycemia and was transferred to the medical intensive care unit (MICU) for monitoring. She reported poor appetite and food intake in the past week and endorsed consuming one alcoholic beverage the night before. Case 2—A 61 year old female with a history of heroin and cocaine abuse was found by the paramedics at home with a decreased level of responsiveness and blood sugar of &lt;30 mg/dL who also required MICU admission. She endorsed using heroin, cocaine and substantial alcohol 2 days prior to admission at a party. She reported 2 episodes of hypoglycemia in the past requiring hospitalization, with no known cause. Kidney and liver disease were ruled out in both subjects. A thorough history including illicit drug use and critical blood samples at the time of hypoglycemia including drug toxicity screen, sulfonylurea screen were obtained. Labs demonstrated an insulin-mediated hypoglycemia and positive sulfonylurea screen for glipizide in both patients. Results: Because of their non-diabetic status, their compelling history and the results of their comprehensive laboratory work-up, we conclude that these subjects had a common exposure- insufflation of heroin contaminated with an oral hypoglycemic agent shortly before their admissions with critical hypoglycemia and clinical instability. Conclusions: This is the first report of hypoglycemia related to inhalation of heroin adulterated with the sulfonylurea glipizide. Frequently heroin is intentionally mixed with other agents (diphenhydramine) to increase the volume for sale, optimize the drug uptake or to ease the side effects. These cases highlight the importance of obtaining a thorough clinical history including potential illicit drug use, acquiring timely and appropriate laboratory samples for toxicologic analysis, and interpreting the findings to curb a potentially deadly epidemic.
Presentation: Saturday, June 17, 2023
SAT436 Endocrine Disruptor Of Organochlorine Pesticides Levels In Saudi Arabian Produce
Authors: Alokail Majed S , Al-Daghri Nasser M , Alnaami Abdullah M , Sabico Shaun , Hussain Syed D , Amer Osama E , Abd-Alrahman Sherif H 
Published: October 2023

Abstract
Disclosure: M.S. Alokail: None. N.M. Al-Daghri: None. A.M. Alnaami: None. S. Sabico: None. S.D. Hussain: None. O.E. Amer: None. S.H. Abd-Alrahman: None.
Food monitoring (FM) is a system used to evaluate and monitor hazardous contaminants, including pollutants such as organochlorine pesticides (OCPs). Long term exposure to organochlorine pesticides (OCPs) can lead to a variety of endocrine and reproductive disruptors including gonadal changes, changes in reproductive behavior, reduced sperm quality, an increase in organ malformations, testicular failure, fetal defects, thyroid dysfunction, and lactation. The present study aimed to determine and quantify OCPs in different local produce collected from different regions in Saudi Arabia. A total of 179 local produce samples were obtained in four regions in Saudi Arabia: Riyadh (N=55), Qassim (N=61), Eastern province (N=38) and Western region (N=25). Solid phase extraction method (QuEChERS) was used to detect OCP residues in samples and levels were quantified using gas chromatograph-electron capture detector (GC-ECD). The results have shown that a total of 11 OCPs were detected overall (9 OCPs in Qassim, Eastern province and Riyadh; 8 in Western region). Levels of alpha BHC was highest in Riyadh; 6 OCPs were highest in Qassim (Beta-BHC, Delta BCH, Dieldrin, Gamma-BHC, heptachlorepoxide and heptachlor); 4 OCPs were highest in the Eastern province (DDD, DDE, endosulfan and endrin), with endrin and endosulfan having the highest levels among all OCPs assessed. A total of 6 OCPs were found in all regions at varying concentrations (Beta-BHC, DDE, Delta-BCH, Dieldrin, endosulfan and heptachlor. Worthy to note is that heptachlorepoxide was found only in Qassim. In conclusion, the endocrine disruptor pesticides such as OCP residues require further investigation for a possible etiologic role in some hormone related cancers such as breast cancer.
Presentation: Saturday, June 17, 2023
SAT439 Euglycemic Diabetic Ketoacidosis When Combining Empagliflozin With Cocaine
Authors: Squicimari-de Cardenas Fabio Alejandro , Bosques-Lorenzo Jaymilitte , Alejandro Loyola-Velez , Rodriguez Cyndia , Carlos Cortes-Sanchez , Colon Castellano Janet Marie 
Published: October 2023

Abstract
Disclosure: F.A. Squicimari-de Cardenas: None. J. Bosques-Lorenzo: None. L. Alejandro: None. C. Rodriguez: None. C. Carlos: None. J.M. Colon Castellano: None.
Background: Euglycemic DKA (eu-DKA) is a life-threatening emergency that can occur in patients with either type 1 or type 2 DM, and manifests as a milder degree of hyperglycemia with glucose levels around 200mg/dL. Cocaine abuse alone has been associated with DKA and eu-DKA by inducing cortisol, epinephrine, and norepinephrine release from adrenal glands, and by its anorexigenic effects by suppressing the feeding centers in the central nervous system. Here we present a case of eu-DKA in a patient that combined SGLT2i with cocaine. Clinical Case: A 66 y/o male with past medical history significant for DM type 2 treated with empagliflozin 25mg daily, metformin 1000mg BID, glargine 45 units am and pm, and exenatide 2mg. Patient presented to the ER with general malaise, dyspnea, abdominal pain, and nauseas. On initial evaluation, vital signs were remarkable for temperature at 97.8 F, pulse at 101 bpm, blood pressure 172/113 mmHg, respiratory rate at 20 bpm. Physical examination significant for a tachypneic, restless, and acutely ill patient that was alert, oriented and able to provide medical history. He and his family members denied him using illicit drugs or alcohol. Laboratories were found with severe metabolic acidosis. Central CO2 at 3.8 mEq/L (24-32 mEq/L), central glucose 241 mg/dL (70-99 mg/dL), elevated anion gap at 29.2 mEq/L, B-hydroxybutyrate markedly elevated at &gt;83.3 mg/dL (0.2 - 2.81 mg/dL), arterial blood gases with pH at 7.11 (7.38-7.46) and HCO3 at 3.0 mmol/L (21-29 mmol/L). Urinalysis was positive for ketones and glucosuria. Toxicology came back positive for cocaine, and negative for alcohol. Due to patients’ severe acidosis and concerns for cardiac arrest, he was intubated for airway protection and admitted to the ICU for further management. DKA protocol was initiated and treatment with IV insulin, IV 5% Dextrose, 0.45% normal saline, potassium replacement, and IV bicarbonate provided until anion gap closed and acidosis resolved. Eventually, patient was successfully extubated and transferred to ward for further management and diabetic treatment optimization. Conclusion: Cocaine use is an independent trigger for DKA and eu-DKA. Euglycemic DKA has been raising with the surge of SGLT2i. As in our patient, concomitant use of SGLT2i and cocaine can precipitate patients for development for DKA/eu-DKA. It is important to educate patients to avoid concomitant use of this two and to perform toxicology screening in patients presenting with DKA or eu-DKA.
Presentation: Saturday, June 17, 2023