bluuebunny/crossref_metadata_2025_split huggingface dataset:
8462 Synergistic Outcomes Of hCG And GLP1-RA Combination Therapy: Improved Body Composition And Carbohydrate Metabolism
Authors: Comite Florence , O’Malley Kaleigh 
Published: October 2024

Abstract
Disclosure: F. Comite: None. K. O'Malley: None.
Objective: Precision medicine prevents and reverses diseases of aging by way of systematic analysis of body composition and extensive blood biomarkers. Andropause, the age-related reduction of free testosterone (FT) in males, elicits symptoms primarily of muscle loss, decreased libido, and diminished energy. Exogenous testosterone therapy (TTx) subsequently increases lean body mass (LBM) and improves both libido and energy levels in affected males. More recently, stimulation of endogenous testosterone from the testes, human Chorionic Gonadotropin (hCG) has emerged as a compelling physiologic alternative to TTx. Common comorbidities to andropause are DMII and/or obesity. Recent literature surrounds the use of GLP-1 receptor agonists to improve insulin sensitivity in these disorders of carbohydrate metabolism. A primary benefit secondary to GLP-1 use is reduction of fat mass; however, concerns of this monotherapy surround loss of muscle.[1] Remarkably, when treated adjunctly with GLP-1s, hCG therapy significantly mitigates muscle loss while maintaining optimal carbohydrate biomarkers. The efficacy and benefits of hormonal optimization through hCG therapy simultaneous to GLP-1 intervention were investigated. Methods: In this retrospective analysis, a cohort of 20 males ≥30 years of age were reviewed at baseline timepoints and 18 months post treatment-initiation. Participants underwent biweekly hCG and weekly GLP-1 subcutaneous injections. Exclusion criteria restricted use of alternative GLP-1/GIP combination medication. Paired T-Tests were used to determine a relationship between LBM, FT, percent body fat (PBF), fasting glucose (FG), fasting insulin (FI), and HbA1c at each timepoint. Results: Body composition analysis as shown via bioelectrical impedance proved baseline PBF (mean=24.60) significantly reduced post-treatment (p&lt;0.05, mean=18.08) for all participants. In addition, relevant carbohydrate metabolic biomarkers FG, FI, and HbA1c provided significant reductions (p&lt;0.05). Initial FT (mean=67.76) and LBM (mean=150.36) increased significantly at follow-up (p&lt;0.05) with values of 167.55 and 154.91, respectively. Discussion: Using metrics of precision medicine, our interpretation reveals a promising combination therapy for males experiencing andropause. The novel use of hCG to optimize FT levels enhances muscle, while simultaneously, fat loss and reversal of harmful carbohydrate metabolic markers resultant from GLP-1 therapy are achieved. Muscle loss due to overall weight loss is thus ameliorated. Our findings merit further investigation of the magnitude of downstream improvements, particularly in energy and libido. References: John P.H. Wilding, e. a. (2021). Once-Weekly Semaglutide in Adults with Overweight or Obesity. The New England Journal of Medicine.
Presentation: 6/3/2024
8439 Targeting Interferon Gamma-Mediated CXCL16-CXCR6 Chemokine-Receptor Interactions As A Strategy To Prevent Immune Checkpoint Inhibitor Autoimmune Diabetes
Authors: Wang S , Huang N , Ortega J G , Lee J , Kimbrell K , Nguyen J , Olay J , McCarthy E , Peluso E , Chen H C , Lechner M G 
Published: October 2024

Abstract
Disclosure: S. Wang: None. N. Huang: None. J.G. Ortega: None. J. Lee: None. K. Kimbrell: None. J. Nguyen: None. J. Olay: None. E. McCarthy: None. E. Peluso: None. H. Chen: None. M.G. Lechner: None.
Autoimmune diabetes mellitus is a rare but life-threatening side effect of immune checkpoint inhibitor (ICI) cancer therapy. Checkpoint inhibitors increase immune activation by blocking regulatory molecules on T cells, including programmed death protein (PD1). As a result of this heightened immune activation, patients can develop autoimmunity in healthy tissues, known as immune related adverse events (IRAEs). ICI-associated diabetes mellitus (ICI-T1DM) is an IRAE that results in autoimmune destruction of insulin-producing pancreatic beta-cells. Patients with ICI-T1DM require life-long insulin therapy and more than half present initially with diabetic ketoacidosis. Unfortunately, the mechanism of this IRAE is not fully understood. Anti-PD1 antibody treatment (10mg/kg/dose, twice weekly, i.p.) of male and female non-obese diabetic (NOD) mice leads to autoimmune infiltrates in multiple tissues, including accelerated insulitis and DM. Single cell RNA sequencing of islet infiltrating immune cells from ICI-treated mice previously showed a role for CD8+ T cells and cytokine interferon gamma (IFNγ) in the development of ICI-T1DM. Using CellChat to perform receptor-ligand interaction analysis of these data, we identified both CD8+ and CD4+ T cells as the primary source of IFNγ in immune infiltrates and islet myeloid cells as the primary target. Furthermore, CellChat analysis showed increased receptor-ligand interactions between T cell receptor CXCR6 and its chemokine CXCL16, as well as CXCR3 and chemokines CXCL9 and CXCL10. In vitro IFNγ stimulation of myeloid cells induced strong expression of CXCL16, 9, and 10, suggesting a potential mechanism by which effector T cells are recruited to islets during ICI therapy. Immunophenotyping of islet-infiltrating immune cells indeed showed increased IFNγ+CXCR6+ effector CD8+ cells in anti-PD1 treated mice compared to isotype-treated controls. Moreover, these IFNγ+CXCR6+CD8+ T cells stained positively for the NRP-V7 mimotope tetramer, a known antigen for CD8+ T cells in spontaneous autoimmune diabetes in NOD mice, suggesting this as an antigen-specific population contributing to the immunopathogenesis of ICI-T1DM. Finally, genetic deletion of CXCR6 in NOD mice delayed the onset of autoimmune diabetes during anti-PD1 treatment in female (p=0.0162) but not male mice (p=0.3656). In summary, these data further elucidate the cellular mechanisms by which IFNγ and chemokine signaling pathways drive the development of ICI-T1DM and identify the CXCR6-CXCL16 axis as a potential therapeutic target to prevent this IRAE in checkpoint inhibitor-treated cancer patients.
Presentation: 6/2/2024
6905 The Necessity For New Criteria To Evaluate Overbasalization In East Asian Patients With Type 2 Diabetes Using Basal Insulin
Authors: Jang Han Na 
Published: October 2024

Abstract
Disclosure: H. Jang: None.
Background: Overbasalization, which refers to adjusting the dose of basal insulin beyond an appropriate dose, should be avoided when using basal insulin in patients with type 2 diabetes. It is recommended to evaluate overbasalization when the basal insulin dose exceeds 0.5 units/kg/day or when post-meal glucose levels are &gt; 180 mg/dL. However, this is an expert opinion, and specific criteria for East Asians have not been presented. Methods: Patients with type 2 diabetes using basal insulin (insulin glargine U-100, insulin glargine U-300, insulin degludec, NPH) at Seoul National University Bundang hospital from December 2020 to November 2023, with fasting plasma glucose (FPG) levels between 80 mg/dL and 130 mg/dL, were retrospectively analyzed. Patients with CKD ≤ grade 3b (estimated glomerular filtration rate &lt; 45 mL/min/1.73m2), those taking medications such as steroids that may affect blood glucose levels, and patients undergoing cancer treatment were excluded. Results: A total of 548 patients were analyzed. The mean age of the subjects was 64.7 ± 12.4 years, with 299 (54.6%) being male, and the mean body mass index was 25.1 ± 6.6 kg/m2. The mean duration of diabetes was 18.1 ± 9.6 years. The mean HbA1c level was 7.7 ± 1.1%, while the mean fasting plasma glucose and median fasting C-peptide levels were 105.4 ± 13.9 mg/dL and 1.4 [0.8, 2.1] ng/mL, respectively. Insulin degludec being the most commonly administered (279 [50.9%]). The mean 2-hr postprandial glucose was 206.3 ± 64.8 mg/dL, with 350 (63.9%) having 2-hr postprandial glucose &gt; 180 mg/dL. The administered insulin dose was 0.35 ± 0.17 units/kg/day, and 101 (18.4%) had an insulin dose &gt; 0.5 units/kg/day. Conclusion: In East Asian patients with type 2 diabetes receiving basal insulin, although high 2-hr postprandial glucose levels suggest the possibility of overbasalization, the administered dosage of basal insulin was relatively low. Considering the lower insulin secretion capacity in East Asians, it is thought that new, specific criteria for overbasalization in East Asians are necessary.
Presentation: 6/3/2024
7064 The Newest LLMs: Can They Help Patients With Diabetic Macular Edema?
Authors: Wu Gloria , Cheng Emily , Rosen Kyler , Zhao Weichen , Wong Adrial , Toram Viki V 
Published: October 2024

Abstract
Disclosure: G. Wu: None. E. Cheng: None. K. Rosen: None. W. Zhao: None. A. Wong: None. V.V. Toram: None.
Background: Cohere and Claude, the newest LLMs, use retrieval augmented generation (RAG) architecture versus ChatGPT and Bard, which use Transformer architecture and can supplement knowledge gaps from the internet. RAG supplements knowledge gaps with vector databases to answer user prompts. Diabetic macular edema is a common visual complication of diabetes. According to the CDC, 38.4 million people have diabetes, and approximately 750,000 Americans have diabetic macular edema and may have vision loss. Due to their prevalence, AI could be applied to address these conditions. Purpose: To evaluate four different LLMs to see which one provides the most accurate information for diabetic macular edema treatment. Methods: We queried Cohere (Coral) + Claude and ChatGPT + Bard. 1) I have diabetic macular edema and I am 40 y/o white male, with 15 years of diabetes and I cannot pass the driving test in California. What will it cost me per year for treatment? I have no health insurance. 2) I am 40 years old, white male, and have had diabetes for 15 years. I was told that I cannot pass the driving test in California. How much will I pay for one year of treatment? I have no health insurance. We use a custom scoring system that has the following metrics. We then take a weighted average: Readability: 20% Accuracy: 40% Helpfulness: 30% Specificity: 10% Results: Cohere Coral: Q1=Read 16/20 | Acc 36/40 | Help 28/30 | Spec 9/10 | Total 89/100 | Q2=Read 14/20 | Acc 34/40 | Help 26/30 | Spec 8/10 | Total 82/100 Claude: Q1=Read 18/20 | Acc 32/40 | Help 26/30 | Spec 7/10 | Total 83/100| Q2= Read 18/20 | Acc 30/40 | Help 25/30 | Spec 6/10 | Total 79/100 ChatGPT: Q1=Read 18/20 | Acc 28/40 | Help 25/30 | Spec 6/10 | Total 77/100| Q2= Readability 18/20 | Acc 28/40 | Help 24/30 | Spec 6/10 | Total 76/100 Bard: Q1=Total 80/100| Q2=Read 16/20 | Acc 30/40 | Help 27/30 | Spec 7/10 | Total 80/100 Cohere Coral consistently provided the most detailed and accurate information, leading with average scores of 85.5/100. Claude, ChatGPT, and Bard followed with scores of 81, 76.5, and 80, respectively. Conclusions: In our small study, RAG-based LLMs can provide accurate and instantaneous health education. Physicians should follow the new, evolving LLMs as it may affect patient education.
Presentation: 6/1/2024
7796 The Profile And Associated Risk Factors Of Diabetic Foot Disease Among Patients With Type 2 Diabetes Mellitus Seen At Outpatient Clinics In A Tertiary Private Hospital In Quezon City, Philippines
Authors: Lopez D C , Lim K T , S. B C , Dampil O C 
Published: October 2024

Abstract
Disclosure: D.C. Lopez: None. K.T. Lim: None. B.C. S.: None. O.C. Dampil: None.
The Profile and Associated Risk Factors of Diabetic Foot Disease Among Patients with Type 2 Diabetes Mellitus Seen at Outpatient Clinics in a Tertiary Private Hospital in Manila, Philippines. Background: Diabetic foot disease is a debilitating complication of diabetes mellitus and is a major source of morbidity, mortality, and reduced quality of life. Determining the risk factors of diabetic foot ulcer is important to prevent the devastating consequences among patients with diabetes. This study aims to determine the profile and associated risk factors of diabetic foot disease among patients diagnosed with type 2 diabetes mellitus being seen in private specialty clinics. Methodology: A single center, analytical cross-sectional study was conducted among patients with type 2 diabetes mellitus at outpatient clinics in a tertiary private hospital in the Philippines. Clinical information and laboratory results were obtained during the time of consult; and patients were classified as either low risk, moderate risk, high risk for diabetic foot disease or in active foot disease. Interaction between various risk factors was explored by multivariate analysis. Results: A total of 129 adult patients with diabetes mellitus were evaluated using the Diabetes Foot Screening and Risk Stratification Tool from January to May 2021. The demographic and clinical profile of the study showed that proportion of patients with neuropathy (χ2=60.66, p=0.001), long duration of diabetes (F=5.92, p=0.004), and low estimated glomerular filtration rate (eGFR) (F=3.70, p=0.023) was significantly higher in patients with moderate to high risk for diabetic foot disease. Univariate polynomial logistic regression analyses showed that neuropathy greatly increased the odds of having moderate (OR=115.63, p=0.001) and high risk stratification (OR=166.50, p=0.001). Other factors were also noted to affect the risk stratification for diabetic foot disease such as duration of diabetes (OR=1.09, p=0.004) and hypertension (OR=2.45, p=0.027). On the other hand, normal eGFR (OR=–1.02, p=0.011), left normal ankle brachial pressure index (OR=–4.32, p=0.042), and good glycemic control (OR=–5.41, p=0.050) significantly decrease the likelihood of having high risk stratification for diabetic patients. Conclusion: Those most susceptible to developing high risk for diabetic foot disease were patients with neuropathy, hypertension, and long duration of diabetes. High-risk patients with the given profile should be followed closely in order to prevent complications brought by diabetes. Keywords:Diabetes mellitus, Diabetic foot disease, Foot ulcer
Presentation: 6/3/2024
8343 The Role Of Pancreatic Nerve Activity On The Development Of Beta Cell Dysfunction With The Macrophage-Beta Cell Interaction
Authors: Yu J , Wang Y , Sha L 
Published: October 2024

Abstract
Disclosure: J. Yu: None. Y. Wang: None. L. Sha: None.
Islet inflammation is a vital factor to the beta cell dysfunction which is driven by inflammatory cytokines TNF-α and IL-1β released by resident macrophages. Pancreatic nerve innervates islet function and our previous study suggested that pancreatic nerve activity might involved in the development of pancreatic beta cell dysfunction. However, it is not known whether pancreatic nerve activity modulates macrophage activity and contributes to the macrophage - beta cell interaction. The aim of our study was to investigate the role of nerve activity on it and the possible mechanism. Methods: Sprague Dawley Rats and high fat diet-induced obese rates were used. An intrapancreatic nerve truck with its intact innervated pancreatic islets were used for the study. The nerve activity was evoked with electric nerve stimulation and insulin and ATP released by beta cells, TNF-α released by macrophages, and IL-1β released mainly by macrophages were measured with nerve activation. Results: Insulin secretion was induced significantly with the nerve activation (8 Hz). With nerve activation, ATP level was significantly increased by 25.5 ± 11.7%. The increased releases of insulin and ATP were abolished with cholinergic M receptor blocker atropine. With nerve activation, TNF-α and IL-1β levels were increased by 25.3±7.6% and 51.8±11.7%, respectively (p&lt;0.05). Interestingly, the increases of TNF-α and IL-1β with nerve activation were also blocked by atropine. Since it is known that acetylcholine does not induce pro-inflammatory cytokine release in macrophages, we suspected that the nerve activity induced TNF-α and IL-1β releases were indirect. ATP is likely a candidate for the indirect effect as receptors. With applying Suramin, a ATP receptor blocker, nerve activation increased TNF-α release was inhibited significantly and IL-1β release was trended to inhibited. atropine, an M receptor blocker, compared with the Control group, decreased by 88.0±3.7% and 63.1±19.6%, respectively (p&lt; 0.01). In obese rats, nerve activation increased TNF-α and IL-1β content by 68.1 ± 22.6% and 39.7 ± 7.4%, respectively, and suramin significantly inhibited the nerve activation induced increase of TNF-α release and trended to inhibit IL-1β release. Conclusion: Our results suggested that the pancreatic nerve activity contribute to the macrophage-beta cell interaction in the development of beta cells dysfunction by enhancing ATP release from islet beta cells.
Presentation: 6/3/2024
8668 Total And Trunk Body Fat Are Associated With Chronic Kidney Disease Progression In Type 2 Diabetes Patients: A Prospective Study
Authors: Zelmanovitz T , Weber D , Pavinatto C , Bello G , de Souza M R , Junior R B , Azevedo M , Dama B L , Silveiro S 
Published: October 2024

Abstract
Disclosure: T. Zelmanovitz: None. D. Weber: None. C. Pavinatto: None. G. Bello: None. M.R. de Souza: None. R.B. Junior: None. M. Azevedo: None. B.L. Dama: None. S. Silveiro: None.
Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease and obesity is considered an independent risk factor for the development and progression of this complication. However, BMI alone, the most commonly used measure to assess adiposity, may not be enough to identification of high risk patients. The ideal markers of adiposity in these patients still need to be better determined. The aim of this study was to evaluate the association between the progression of DKD in type 2 diabetes patients and the following body adiposity markers: BMI, waist circumference (WC) and estimated total and trunk body fat. Research design and methods: In this prospective cohort study, at baseline, type 2 diabetes outpatients were submitted to percentage body fat (PBF) evaluation estimated by bioelectrical impedance (BIA; InBody 230, Biospace, Korea) as well as Dual Energy X-Ray Absorptiometry (DXA; Lunar - iDXA), as a reference standard. Clinical evaluation consisted of glycemic and lipid profile, blood pressure control and the search for diabetic chronic complications. Urinary albumin was measured twice and estimated glomerular filtration rate (eGFR) was estimated by using the CKD-EPI equation. The progression of DKD was defined by the presence of at least one of the following: worsening of albuminuria, a decline of eGFR ≥ 5 ml/min/1.73m2 per year, a decline in eGFR of ≥ 40% from baseline or kidney failure defined by sustained eGFR &lt; 15 ml/min/1.73m2. Results: A total of 201 patients with type 2 diabetes (aged 63 ± 9 years; 42% male), were followed during 6 years. In a multivariate Cox regression analysis, the PBF was associated with progression of DKD (HR=1.04, 95% CI: 1.008 - 1.08; P= 0.015), adjusted for age, gender, using ACE inhibitors or angiotensin receptor blockers, and systolic blood pressure values. In a different model, percentage of trunk fat was also associated with progression of DKD (HR=1.05, 95% CI: 1.02 - 1.09; P= 0.003), adjusted for the same covariates. No association was observed with BMI and WC. Conclusion: In patients with type 2 diabetes, percentage total and trunk body fat, as markers of body adiposity, seem to be associated with progression of DKD. Confirming these findings with further studies, it could provide one more tool in the evaluation and management of a modifiable risk factor of this complication.
Presentation: 6/1/2024
8158 Transient Blindness In Metformin-Associated Lactic Acidosis
Authors: Abouelkheer Y , Nasir A , Ibrahem M 
Published: October 2024

Abstract
Disclosure: Y. Abouelkheer: None. A. Nasir: None. M. Ibrahem: None.
Transient Blindness in Metformin-associated Lactic Acidosis Background: Metformin-associated lactic acidosis (MALA) is a rare side effect of metformin use. MALA can result in acute transient blindness in patients with severe metabolic derangements. Clinical Case: A 62-year-old woman presented with severe diarrhea, poor oral intake, malaise, and vomiting on a background of metformin-treated type 2 diabetes mellitus. Laboratory investigations showed bicarbonate &lt;2 mmol/L, anion gap 48 mmol/L, lactic acid 20.5 mmol/L, serum osmolality 352 mOsm/kg, negative urine toxicology screen, and positive SARS-CoV-2. In the emergency department, the patient developed sudden onset bilateral vision loss. The examination was remarkable for complete vision loss bilaterally in all fields, associated with minimally reactive pupils and spontaneous ocular movements with an otherwise unrevealing neurological examination. Computed Tomography (CT) of the brain with stroke protocol showed no evidence of acute intracranial process. CT angiogram of the brain and neck showed patent intracranial and cervical vasculature without high-grade stenosis, large vessel occlusion, or aneurysm. While receiving medical management with intravenous fluid resuscitation and sodium bicarbonate supplementation, the patient had a spontaneous return of vision with no additional neurological complications or deficits. The severe metabolic derangements were associated with distributive shock, requiring admission to the intensive care unit for urgent hemodialysis, pressor support, empiric antibiotics, and stress-dose steroids. Shortly after the patient’s only hemodialysis session, we noted the resolution of her critical metabolic disturbances, renal failure, and shock state. Laboratory investigations post-dialysis showed bicarbonate 12 mmol/L, anion gap 36 mmol/L, and lactic acid 10.5 mmol/L. Follow-up MRI showed chronic lacunar infarct of the left basal ganglia, and she was discharged home six days later. Conclusion: Transient blindness in MALA can mimic acute neurovascular events. Prompt correction of metabolic derangements can aid in reversing systemic symptoms and blindness. Reference: DeFronzo R, Fleming GA, Chen K, Bicsak TA. Metformin-associated lactic acidosis: Current perspectives on causes and risk. Metabolism. 2016;65(2):20-29. doi:10.1016/j.metabol.2015.10.014
Presentation: 6/2/2024
Data flow in clinical laboratories: could metadata and peridata bridge the gap to new AI-based applications?
Authors: Padoan Andrea , Cadamuro Janne , Frans Glynis , Cabitza Federico , Tolios Alexander , De Bruyne Sander , van Doorn William , Elias Johannes , Debeljak Zeljko , Perez Salomon Martin , Özdemir Habib , Carobene Anna 
Published: October 2024

Abstract
In the last decades, clinical laboratories have significantly advanced their technological capabilities, through the use of interconnected systems and advanced software. Laboratory Information Systems (LIS), introduced in the 1970s, have transformed into sophisticated information technology (IT) components that integrate with various digital tools, enhancing data retrieval and exchange. However, the current capabilities of LIS are not sufficient to rapidly save the extensive data, generated during the total testing process (TTP), beyond just test results. This opinion paper discusses qualitative types of TTP data, proposing how to divide laboratory-generated information into two categories, namely metadata and peridata. Being both metadata and peridata information derived from the testing process, it is proposed that the first is useful to describe the characteristics of data, while the second is for interpretation of test results. Together with standardizing preanalytical coding, the subdivision of laboratory-generated information into metadata or peridata might enhance ML studies, also by facilitating the adherence of laboratory-derived data to the Findability, Accessibility, Interoperability, and Reusability (FAIR) principles. Finally, integrating metadata and peridata into LIS can improve data usability, support clinical utility, and advance AI model development in healthcare, emphasizing the need for standardized data management practices.