bluuebunny/crossref_metadata_2025 huggingface dataset:
SAT049 Goldfish LEAP2: Molecular Cloning, Functional Characterization, And Novel Regulation By IGF And Insulin At The Hepatic Level
Authors: Jin Fanming , Qin Xiangfeng , Ye Cheng , He Mulan , On-Lam Wong Anderson
Published: October 2023

Disclosure: F. Jin: None. X. Qin: None. C. Ye: None. M. He: None. A.O. Wong: None.

Liver-expressed antimicrobial peptide 2 (LEAP2) is a peptide highly expressed in the liver and its secretion induced by bacterial infection constitutes an integral component of innate immunity in vertebrate species. Recently, LEAP2 has been confirmed to be the endogenous antagonist of the feeding regulator ghrelin, implying that the peptide may play a role in appetite control and energy homeostasis. However, whether LEAP2 can be regulated by metabolic/endocrine signals is still unclear and the signal transduction involved is totally unknown. Using goldfish as a model, three isoforms of LEAP2, namely LEAP2a, 2b & 2c, have been cloned and phylogenetic analysis confirmed that they could be clustered into the clade of fish LEAP2. Comparative synteny also revealed that the three isoforms were derived from separated genes with similar structural organization but located in different chromosomes of goldfish genome. The a.a. sequences and 3D protein structure of LEAP2a-c were found to be highly comparable with LEAP2 of other vertebrates and tissue expression profiling by RT-PCR also showed that they were expressed at high levels in the liver but to a lower extent in other tissues. As members of antimicrobial peptides, goldfish LEAP2a-c not only could exhibit antimicrobial activity against Staphylococcus epidermidis but also play important role in fish innate immunity, which is evidenced by their transcript expression induced by LPS & cytokines at hepatic level as well as in immune tissues in goldfish naturally infected with Aeromonas hydrophila. In goldfish liver cells, transcript expression of LEAP2a-c could be up-regulated in a time- and dose-dependent manner by IGF-I, IGF-II and insulin. Using a pharmacological approach, the stimulatory effects of IGF-I/-II and insulin on the three isoforms of LEAP2 were confirmed to be mediated by IGF-I receptor (IGF1R) but not insulin receptor activation. Furthermore, the PI3K/Akt, MEK/ERK and P38 MAPK pathways were shown to be involved in IGF-I induced LEAP2a-c gene expression. Our findings for the first time demonstrate that the endocrine signals targeting the liver (insulin) or produced locally within the liver (IGF-I & -II) can play a role in regulating LEAP2 expression at the hepatic level, which may shed light on a novel aspect of the functional crosstalk between innate immunity and feeding control/energy balance in fish model.

Presentation: Saturday, June 17, 2023
SAT058 Diabetes Complicated By DKA, Mucormycosis And Covid-19
Authors: Gordon Ashley
Published: October 2023

Disclosure: A. Gordon: None.

Background: Mucormycosis is an invasive opportunistic fungal infection, that although rare, has an estimated all-cause mortality of 54%. Even with aggressive treatment, significant tissue necrosis and bone destruction can occur. Risk factors include diabetes, acidosis (as in diabetic ketoacidosis), excess iron, transplant, malignancy, kidney and liver disease, immunosuppressant and corticosteroid use - and in more recent times, the Covid-19 infection. We present a case of invasive rhino-orbital cerebral mucormycosis in the setting of DKA, uncontrolled diabetes and Covid-19. Case: A 60-year-old female with history of uncontrolled type 2 diabetes (HbA1c 14.3%) presented after being found unresponsive. Her exam was significant for encephalopathy, complete left eye ophthalmoplegia and right-sided hemiparesis. She was hemodynamically stable without fever. Initial labs showed significant hyperglycemia with an elevated anion gap and beta-hydroxybutyrate indicative of diabetic ketoacidosis (DKA). She had a lumbar puncture which showed leukocytosis with neutrophilia (146 WBC, 39% neutrophils), elevated glucose and normal protein; CSF culture was negative for growth. She also tested positive for Covid-19 although CXR was unremarkable and she did not require treatment. Initial CT/CTA head/neck showed complete occlusion of the left cervical internal carotid artery with associated acute/subacute infarcts in the left frontal, parietal, temporal and occipital lobes. CT sinuses showed severe frontal, maxillary and ethmoid sinus mucosal wall thickening with left premaxillary soft tissue swelling and leftward nasal septum deviation. Finally, orbital imaging showed left cavernous sinus thrombosis, left superior ophthalmic vein thrombosis, and necrosis vs devascularization of the extraocular muscles. She was initially treated with fluids, an insulin infusion and broad-spectrum antibiotics and was evaluated by neurology, ophthalmology, infectious disease and otolaryngology. She underwent surgical debridement with left maxillary antrostomy, left total ethmoidectomies and septoplasty. Sinus cultures were positive for MSSA (methicillin sensitive staph aureus) and tissue pathology showed angioinvasive fungal disease compatible with Mucor/Rhizomucor species. Antimicrobial coverage was changed to intravenous Nafcillin and Amphotericin B, and she underwent further surgical debridement twice more. Repeat brain imaging to evaluate for disease progression is pending. Discussion: Early detection and aggressive treatment of Mucormycosis with surgical debridement and Amphotericin B can improve patient outcomes, however the mortality rate is still significant. Therefore, tight glycemic control in high risk groups is imperative, particularly in those with uncontrolled diabetes complicated by DKA and Covid-19 infection (with or without steroid treatment).

Presentation: Saturday, June 17, 2023
SAT061 Deficiency Of ENaC Excites Pancreatic β Cells To Promote Insulin Secretion
Authors: Que Yanting , Ma Xiyang , Wu Yong , Chen Junjiang , Guo Jinghui , Chun Ruan Ye
Published: October 2023

Disclosure: Y. Que: None. X. Ma: None. Y. Wu: None. J. Chen: None. J. Guo: None. Y. Ruan: None.

In response to glucose elevation or other physiological stimuli, pancreatic islet β cells are excited to mobilize intracellular Ca2+ leading to insulin secretion, which is a complex cellular event with underlying mechanisms not fully elucidated. The present study explored possible involvement of the epithelial Na+ channel (ENaC) in β cell excitability and insulin secretion. Analyzing human databases, primary rat/mouse pancreatic tissues as well as RINm5F, a rat β-cell line, we confirmed the expression of Scnn1a, Scnn1b and Scnn1g genes (encoding ENaC subunits, α, β and γ, respectively) in human and rodent β cells. To our surprise, inhibiting this Na+ channel by selective blockers, amiloride (1-10 µM) or benzamil (1 µM), did not retard insulin secretion, but instead triggered a slow membrane depolarization with electrical bursts (41.5 ± 5.9 mV, measured by patch-clamp, n = 5-6), elicited substantial Ca2+ oscillations (135.2 ± 2.5% of baseline, by Fura-2 imaging, n = 256-380) and promoted insulin secretion (158.2 ± 25.6% of control, by ELISA, t-test, p < 0.05, n = 6) in RINm5F or isolated mouse β cells. siRNA-based knockdown of ENaCα, the rate-limiting subunit of ENaC, in RINm5F cells confirmed that deficiency of ENaC induced a significant increase in insulin secretion (230.2 ± 20.2% of control, t-test, p < 0.001, n = 6). Proteomic analysis of RINm5F cells (n = 5) through mass spectrometry showed that signaling pathways key to glucose metabolism and insulin secretion were significantly activated in RINm5F cells with ENaC knockdown in comparison with control cells, consistently suggesting a role of ENaC deficiency in exciting β cells to release insulin. We next built a mouse model with β cell-speciﬁc knockout of ENaCα (Scnn1afl/fl, Ins1-Cre+), which exhibited disturbed responses in glucose tolerance test in comparison with the loxp-negative Cre control mice (Scnn1awt/wt, Ins1-Cre+). Taken together, these results have suggested an important role of ENaC in regulating the excitability of β cells and insulin secretion, which may contribute to the understanding of Na+ environment in relation to insulin homeostasis. This work was supported in part by National Natural Science Foundation of China (82071599), Areas of Excellence Scheme of Hong Kong (AoE/M-402/20) and Bai Cheng Bai Yuan Start-up Fund (I2022A008).

Presentation: Saturday, June 17, 2023
SAT063 Dopaminergic Agonist Cabergoline Inhibits Autophagic Flux In Beta Pancreatic Cells
Authors: Francisco Mendez Luis , Etcheverry Boneo Luz , Becu-Villalobos Damasia , Sorianello Eleonora
Published: October 2023

Disclosure: L.F. Mendez: None. L. Etcheverry Boneo: None. D. Becu-Villalobos: None. E. Sorianello: None.

Autophagy is a lysosomal degradation process necessary for the maintenance of cellular homeostasis, which is based on constantly removing ubiquitinated proteins and dysfunctional organelles that are eventually toxic to the cell. Since alteration of this process in pancreatic beta cells can lead to the development of diabetes, autophagy modulators arise as interesting therapeutic compounds for the treatment of this prevalent human pathology. Previous studies indicate that activation of the dopamine D2 receptor (D2R) alters autophagy in several cell types. In this context, we aimed at determining the effect of D2R activation by its agonist Cabergoline (CAB) on the autophagic process in pancreatic beta cells. To that end, we stimulated the murine pancreatic beta cell line MIN6B1 with 10-5 M CAB for 1, 6 and 24h to evaluate the kinetics of autophagic vesicle formation. Additionally, 10-5 M CAB in the presence or absence of Chloroquine (CQ), an inhibitor of late stages of the autophagy process, was used to study the autophagic flux. Using Western Blot and immunofluorescence and confocal microscopy, the autophagy markers LC3 (autophagic vesicle marker) and p62/SQSTM1 (autophagy cargo receptor and degradation substrate) were analyzed. CAB increased LC3 nucleation as a function of stimulation time, showing significant differences relative to the control after 6h (one-way repeated measures ANOVA p=0.0038; Tukey: Control vs CAB6h p<0.05, vs CAB24h p<0.01). Moreover, CAB significant increased p62/SQSTM1 levels after 24h of stimulation (one-way repeated measures ANOVA: p=0.0157; Tukey: Control vs CAB24h p<0.05). When studying the effect of CAB on the autophagic flux, we observed that CQ significantly increased LC3 and p62/SQSTM1 levels at 24h of incubation (two-way repeated measures ANOVA (CQ and CAB): for LC3: interaction p<0.05, Tukey: CQ vs Control p<0.0001; for p62/SQSTM1: CQ pretreatment effect p<0.05), as expected. Interestingly, CAB diminished the accumulation of LC3 (Test-T Delta (CQ-Control) vs Delta (CQCAB-CAB): p=0.04) and p62/SQSTM1 (Test-T Delta (CQ-Control) vs Delta (CQCAB-CAB): p=0.01) elicited by CQ at 24h. We conclude that CAB is able to increase autophagic vesicle formation and, in addition, to decrease autophagic flux after 24h of stimulation in MIN6B1 pancreatic beta cells. This work was funded by CONICET, ANPCyT, Fundación René Barón and Fundación Williams.

Presentation: Saturday, June 17, 2023
SAT067 Bone Marrow-induced Epithelial-Mesenchymal Transition In Beta Cells
Authors: Lee Jihyun
Published: October 2023

Disclosure: J. Lee: None.

Normal cellular function is achieved via regulated cell differentiation cues. Deregulation of these intricately wired processes promotes cellular dysfunction. The pancreatic islet beta cell (β-cell) is a prime example of such integration between optimal cell differentiation and function. Fully differentiated adult β-cells synthesize and secrete insulin. But some express more than one single hormone, and cells containing insulin and glucagon (Ins+:Glu+ cells) are seen during prenatal pancreas development. Interestingly, Ins+:Glu+ cells have been observed in adult islets from diabetic mice or type 2 diabetes (T2D) human cadavers. It is still unclear the origins and relevance of these Ins+:Glu+ cells, and whether this phenomenon is a benefit in the context of severe β-cell stress. But, growing evidence suggests that Ins+:Glu+ cells represent attempts made by the mature β-cell to return to an immature stage with the goal of proliferating and reconstituting depleted β-cell reservoir when faced with a metabolic challenge. In this study, we thus investigated whether adult β-cells undergo epithelial to mesenchymal transition (EMT) that allows β-cells to retrace the developmental steps and attempt β-cell functional recovery. EMT can be induced by many growth factors and cytokines activated when epithelial cells encounter specific signals released by their immediate neighbors. The bone marrow microenvironment can activate EMT in adjacent cells through the secretion of chemokines, cytokines, and growth factors. We postulated bone marrow cells (BMCs) could induce EMT in β-cell. To accomplish this goal, we have developed islet cell and bone marrow cell co-culture conditions. Islets and bone marrow cells obtained from normal chow diet (NCD) and high-fat diet-fed (HFD) mice as well as specimens from non-diabetic and T2D humans are used in co-culture systems. RNA sequencing analysis showed that co-culture pancreatic islet cells with whole bone marrow cells induced the expression of genes relative to mesenchymal cells and suppressed beta cell marker genes like MafA, Ins. Results from immunofluorescence staining analysis also revealed that BMCs promoted mesenchymal phenotype in islet β-cells. We found that cytokines known to induce EMT were secreted in the co-culture media. Mice fed with HFD increased levels of that cytokines in serum compared to NCD. We further confirmed that cytokines secreted by BMCs activated EMT in mouse and human islet β-cells. Blocking of cytokines signaling decreased mesenchymal phenotypes in islet β-cells. Overall, our data suggest that EMT of β-cells is regulated by bone marrow cells via crosstalk between bone marrow cells and pancreatic islets using cytokines.

Presentation: Saturday, June 17, 2023
SAT069 Targeting Human β-Cell G Protein-coupled Receptors To Alter Cytokine-mediated Caspase Activation
Authors: dos Santos Karina Rodrigues , Mukherjee Noyonika , Barella Luiz F , Armoo Fiona , Eizirik Decio L , Templin Andrew T , Kalwat Michael A
Published: October 2023

Disclosure: K. Rodrigues dos Santos: None. N. Mukherjee: None. L.F. Barella: None. F. Armoo: None. D.L. Eizirik: None. A.T. Templin: None. M.A. Kalwat: None.

In type 1 diabetes (T1D) autoimmune destruction of pancreatic islet β-cells causes a lack of insulin, leading to hyperglycemia. The development of therapies that can prevent β-cell death is critical. β-cell proliferation and survival pathways are affected by signaling through G protein-coupled receptors (GPCRs). Using high-depth RNA-seq, we found altered expression of 123 different GPCRs in human islets exposed to cytokines (IL1β 50U/ml + IFNγ 1000U/ml, 48 h) to model the T1D milieu. We hypothesized these candidates may be exploited for β-cell protection. Among the candidates, adenosine receptors (ADORA1 and ADORA2A), calcium-sensing receptor (CASR), and metabotropic glutamate receptor 4 (GRM4) stood out. Cytokines decreased the expression of ADORA1 and CASR, but increased ADORA2A and GRM4. To gauge the impact of agonizing/antagonizing these receptors, we pre-treated human EndoC-β H1 β-cells or islets with receptor ligands and co-treated with cytokines (IL1β 50U/ml + IFNγ or IL1β + 1000U/ml IFNγ + 1000U/ml TNFɑ, 48 h) and measured glucose-stimulated insulin secretion, cell viability, and gene expression. Each cytokine combination induced target gene expression (e.g. CXCL10), but only the combination of IL1β + IFNγ + TNFɑ reduced glucose-stimulated insulin secretion. Preliminary experiments indicated that adenosine receptor ligands had little impact in our assays. However, ligands for CASR and GRM4 exhibited significant suppression of cytokine-induced caspase 3/7 activation in EndoC-βH1 cells. Interestingly, suppressed caspase activation did not result in observable impacts on live/dead cell ratios or live-cell analysis using Incucyte in EndoC-βH1 cells. Consistently, we also observed cytokine-mediated cell death in the presence of the pan-caspase inhibitor ZVAD-fmk. We conclude that a variety of β-cell GPCR-mediated signaling pathways may converge to prevent cytokine-induced caspase activation, but additional measures are needed to enable protection from eventual cell death. Our results and this line of investigation is significant because understanding mechanisms of GPCR-cytokine crosstalk in β-cells will inform strategies to protect islets in other models of T1D.

Funding: JDRF 1-INO-2022-1113-A-N and Diabetes Research Connection #33.

Presentation: Saturday, June 17, 2023
SAT071 Inhibition Of 12 Lipoxygenase In A Humanized Mouse Model Of Type 1 Diabetes Delays Progression Of Hyperglycemia
Authors: Nargis Titli , Chakraborty Advaita , Figatner Kayla , Maloney David , Boxer Matthew , Tersey Sarah A , Mirmira Raghavendra G
Published: October 2023

Disclosure: T. Nargis: None. A. Chakraborty: None. K. Figatner: None. D. Maloney: None. M. Boxer: None. S.A. Tersey: None. R.G. Mirmira: None.

Type 1 diabetes (T1D) is an autoimmune disorder characterized by islet inflammation (insulitis). We have recently shown that a key mediator of inflammatory signaling in the islet beta cell is the enzyme 12-lipoxygenase (12-LOX), which generates proinflammatory eicosanoids that augment dysfunctional insulin secretion and beta-cell visibility to the immune system. Whereas inhibition of 12-LOX offers an opportunity to modify T1D progression by altering how the beta cell responds to insulitis, a barrier to testing inhibitors in preclinical models is the specificity of next generation inhibitors toward the human enzyme. To generate a preclinical platform for the study of human-specific 12-LOX inhibitors, we developed a mouse model in which the mouse-equivalent Alox15 coding region was replaced with the human ALOX12 gene, while retaining the mouse upstream control region. These mice (hALOX12) were developed on both the C57BL/6J and NOD genetic backgrounds, then subjected to treatment with the human 12-LOX inhibitor VLX-1005 to evaluate diabetes progression. C57BL/6J-wildtype and C57BL/6J-hALOX12 mice were confirmed to express exclusively mouse Alox15 and human ALOX12, respectively, using RNA isolated from islets. To test susceptibility to toxin-induced diabetes, C57BL/6J-wildtype and C57BL/6J-hALOX12 were subjected to multiple low-dose streptozotocin (STZ) to induce diabetes. Both wildtype and humanized mice exhibited gradual and equivalent hyperglycemia (within 25 days) following STZ injection. Following intraperitoneal VLX-1005 therapy (30 mg/kg), whereas C57BL/6J-wildtype mice developed diabetes (with a delay of 10 days) following STZ, C57BL/6J-hALOX12 mice showed complete protection against STZ-induced diabetes and exhibited significantly better glucose tolerance compared to vehicle- or VLX-1005-injected wildtype controls and vehicle-injected C57BL/6J-hALOX12 mice. Next, hALOX12 mice were backcrossed onto the NOD.ShiltJ background model of autoimmune T1D. NOD-hALOX12 mice received either vehicle or VLX-1005 (30 mg/kg) orally during the prediabetic phase (6-10 weeks of age) and were followed for diabetes incidence. Mice receiving VLX-1005 showed a significant delay with only 30% of female and 7% of male mice developing diabetes over 25 weeks of age. Pancreatic sections from the mice treated with VLX-1005 showed reduced insulitis and increased beta cell mass compared to vehicle controls. In summary, the hALOX12 mouse model serves as a preclinical translational platform to interrogate effects of next generation 12-LOX inhibitors and demonstrates the potential of VLX-1005 to modify T1D disease progression.

Presentation: Saturday, June 17, 2023
SAT092 A Case Of Mature Onset Diabetes Of The Young
Authors: Beshay Lauren , Thakkar Aditi
Published: October 2023

Disclosure: L. Beshay: None. A. Thakkar: None.

Background: Maturity onset diabetes of the young (MODY) is a disorder characterized by noninsulin-dependent diabetes diagnosed at a young age (<25 years) with autosomal dominant inheritance and lack of autoantibodies. It accounts for 2 to 5 percent of diabetes cases. Several different genetic abnormalities have been identified causing disruption in pancreatic beta cells development and function leading to impaired insulin secretion. Mutations in hepatocyte nuclear factor-1-alpha (HNF1A) is the most commonly identified mutation occurring in 52 to 65 of MODY cases. Case Description: A 21 year old female with a history of diabetes and recurrent skin abscesses presented to the emergency room with right lower quadrant epidermal abscess. Endocrinology was consulted for evaluation of her diabetes. She was diagnosed at age 14 when she presented with weight loss, polyuria, polydipsia, BG 406 without diabetic ketoacidosis. She reported a history of type 2 diabetes in mother. Her medications included metformin, lantus and humalog. It was noted that her diabetes was never controlled with an A1c persistently >10%. Patient reported skin swelling with insulin injections and working two jobs which limited her ability to take more than one injection per day. Her BMI is 23 kg/m2. Labs this admission showed HbA1c 13.7%, GAD 65 Ab and IA-2 Ab negative, c-peptide 1.1 ng/ml, with a glucose of 209 mg/dl. MODY was suspected due to her age, intact c-peptide, and lack of DM1 antibodies. The patient was discharged on Trulicity 0.75 mg weekly, Lantus 12U nightly, Glipizide 2.5mg daily. On follow up, a MODY genetic panel confirmed a HNF1A missense variant with AD inheritance. Since initiation of sulfonylurea, she has had improved control of diabetes. Glipizide dose is being titrated up with concomitant decrease in insulin dose with plan to discontinue basal insulin once her blood sugars are at goal. Conclusion: The HNF1A gene on chromosome 12 is a weak transactivator of the insulin gene in beta cells. Mutations of HNF1A can lead to abnormal insulin secretion and a low renal threshold for glucose. These patients are at risk for micro- and macrovascular complications of diabetes. In terms of treatment, they exhibit increased insulin sensitivity and marked sensitivity to the hypoglycemic effects of sulfonylureas compared with patients with type 2 diabetes. Thus, patients can be successfully treated with sulfonylurea monotherapy, and in one clinical study, approximately 70 percent of patients previously treated with insulin successfully switched to sulfonylureas. Thus, it is important to evaluate etiology of diabetes, as detection of MODY variants in which sulfonylureas are used for treatment simplifies management and improves outcomes as demonstrated in this case.

Presentation: Saturday, June 17, 2023
SAT122 The Barriers Of Insulin Access In A Case Of Wolfram Syndrome
Authors: Sacoto Daniel Hernan , Villavicencio Camila Alejandra , Belokovskaya Regina , Franco-Akel Alberto A
Published: October 2023

Disclosure: D.H. Sacoto: None. C.A. Villavicencio: None. R. Belokovskaya: None. A.A. Franco-Akel, MD: None.

Wolfram syndrome (WS) is a rare and fatal condition with a median age of death of about 39 years and affecting around 1 of 100,000 people in North America. Insulin is the mainstay of treatment in WS though, access to it may affect adherence and glycemic control which is correlated with neurodegenerative progression. We present a patient with WS whose complications exacerbated due to insulin access. A 19-year-old African American male with a history of type 1 diabetes mellitus (T1DM), presented to the ED with a 2 day-history of general malaise and emesis. Diabetic ketoacidosis (DKA) (blood glucose 802 mg/dL, pH 7.2, positive serum ketones) was diagnosed upon arrival. Right optic nerve atrophy was diagnosed at age of seven. At age of eight, patient was diagnosed with bilateral sensory-neuronal hearing loss (SNHL) which led to school withdrawal. It was then when suspicion of WS arose. Single nucleotide polymorphism microarray confirmed homozygosity from the region of linkage on chromosome 4p16.1, where the WFS1 gene lies. At the age of eighteen, patient was diagnosed with neurogenic bladder for which he requires frequent self-catheterization. Since his T1DM diagnosis, patient has faced multiple barriers accessing insulin secondary to insurance issues and lack of social support resulting in multiple hospital admissions for DKA and urinary retention episodes. WS is an autosomal recessive disorder resulting from WFS1 or WFS2 gene mutation on chromosome 4p. WS commonly presents as childhood-onset diabetes mellitus, optic atrophy, SNHL, and neurogenic bladder. Insulin is the first line treatment for optimal glycemic control in WS. Despite optimal glycemic control, WS symptoms and neurodegenerative progression may be influenced by other factors. First, treatment access for rare diseases has shown to be impacted by medical unconscious bias, in addition to systemic, linguistic, and socioeconomic challenges patients may face. Furthermore, Medicaid insurance covering rare diseases still varies widely between 15-67%, and in those insured, there is still a 61% chance of delay or denial due to pre-approval requirements. In addition, poor glycemic control has been correlated with lower socioeconomic status, lack of access to devices such as insulin pumps, migratory status, social support and environment, food security, and ethnic background. Since diabetes control in WS patients is paramount to a better quality of life, additional studies are needed to understand the full scope of barriers that can contribute to policies that facilitate better treatment access for patient and families living with WS.

Presentation: Saturday, June 17, 2023
SAT133 A Case Study Of UX/UI Design Diabetes Medication Discharge Orderset: An Initiative To Reduce Discharge Prescribing Error
Authors: Yunasan Elvina , Park Jeayoung , Reddy Rashmi , Pennant Marjorie
Published: October 2023

Disclosure: E. Yunasan: None. J. Park: None. R. Reddy: None. M. Pennant: None.

Prescribing errors involving diabetes medications on discharge are common. The complexity of prescribing insulin, especially due to multiple insulin preparations and supplies contributes to these errors. For example, In our teaching hospital between 01/2021-06/2021, among 40 patients with diabetes mellitus (DM) that were discharged home with insulin, 22 patients (55 %) were discharged without or with incorrect insulin supplies. Well-designed order -set has the potential to reduce the potential of medication errors. Here we present a case study of utilizing FIGMA prototyping software to design a new insulin discharge order set. FIGMA is a web-based user interface design tool, that enables multiple parties to collaborate and work on user experience (UX) and User Interface (UI) prototyping. The aim of this case study is to explore design considerations using FIGMA software for establishing a patient-centered, and user-friendly insulin discharge order set involving multiple stakeholders in the hospital including residents, diabetes educators, attendings, pharmacists, and endocrinologists. We conducted multiple prototyping sessions using FIGMA software. Each participant is able to work simultaneously on the discharge order set together in real-time. The prototyping sessions result in a new discharge order set, which focused on simplicity and provider efficiency in the hope to reduce prescribing errors. Here we outline the advancement in order set design. The previous order set presents 20 different types of insulin pens/syringes that are listed together with a blood glucose meter, testing strips, lancets, alcohol pads, and a lancet device. After that, providers have to manually enter the order for insulin separately. In the new order set, providers will only see 2 options, “Patient uses insulin pen”, and “Patient uses vial and syringe”. When providers choose, “Patient uses insulin pen”, the new order set would automatically pre-selected the options for insulin pen, pen needle, glucometer, testing strips, lancets, and alcohol swabs. Testing supplies options come with default instructions and prefilled quantities. Options for endocrinology, diabetes educator and transitional care referrals are also automatically pre-selected. Additional orders such as metformin, GLP-1 agonist, and SGLT-2 inhibitors are presented as options. Alternatively, if providers choose the insulin syringe option, the order set would look similar, except the order set would present pre-selected options for insulin vials that are already linked with the correct syringe size. In conclusion, creating an insulin discharge order set using FIGMA is a great way to collaborate with multiple stakeholders. This platform can also be potentially utilized in developing other order sets.

Presentation: Saturday, June 17, 2023
A hull reconstruction–reprojection method for pose estimation of free-flying fruit flies
Authors: Maya Roni , Lerner Noam , Ben-Dov Omri , Pons Arion , Beatus Tsevi
Published: October 2023

Understanding the mechanisms of insect flight requires high-quality data of free-flight kinematics, e.g. for comparative studies or genetic screens. Although recent improvements in high-speed videography allow us to acquire large amounts of free-flight data, a significant bottleneck is automatically extracting accurate body and wing kinematics. Here, we present an experimental system and a hull reconstruction–reprojection algorithm for measuring the flight kinematics of fruit flies. The experimental system can automatically record hundreds of flight events per day. Our algorithm resolves a significant portion of the occlusions in this system by a reconstruction–reprojection scheme that integrates information from all cameras. Wing and body kinematics, including wing deformation, are then extracted from the hulls of the wing boundaries and body. This model-free method is fully automatic, accurate and open source, and can be readily adjusted for different camera configurations or insect species.
Έκφραση των ιντερλευκινών στη φλεγμονώδη νόσο του εντέρου πριν και μετά την χορήγηση βιολογικών παραγόντων αλλά και σε υγιείς μάρτυρες
Authors: Τόσκας Αλέξανδρος
Published: October 2023

Οι ιντερλευκίνες θεωρούνται μόρια-στόχοι για μελλοντικές θεραπείες στην ΙΦΝΕ. Οι IL-19 και IL-24 είναι μέλη της οικογένειας της IL-10 και μέσω του JAK-STAT προκαλούν την έκκριση προφλεγμονωδών κυτταροκινών, η ακριβής δράση τους όμως στην εντερική φλεγμονή δεν έχει αποκωδικοποιηθεί. Η IL-21 έχει αποδειχθεί ότι εμπλέκεται στις ανοσιακές απαντήσεις τύπου Th1, Th2 και Th17 ως προφλεγμονώδης κυτταροκίνη. Παρομοίως η IL-33, ρυθμίζει την έκφραση των Th1 κυτταροκινών και την λειτουργία των εντερικών Τ-ρυθμιστικών κυττάρων σε χημικά μοντέλα κολίτιδας και ασθενείς με ΙΦΝΕ. Σε αυτή την μελέτη, η έκφραση των IL-19, IL-24, IL-21 και IL-33, ταυτοποιήθηκε με την χρήση ανοσοϊστοχημείας σε 121 ασθενείς με μέτρια έως σοβαρή ΙΦΝΕ, πριν και μετά από 12 μήνες υπό αγωγή με βιολογικούς παράγοντες. Τα αποτελέσματα αναλύθηκαν στατιστικά με την χρήση SPSS. Μία αυξημένη έκφραση IL-19 βρέθηκε στην ομάδα των ασθενών με ΙΦΝΕ και ΝΚ σε σύγκριση με υγιείς μάρτυρες. Ειδικότερα, στην ομάδα ασθενών με ΝΚ, η έκφραση της IL-19 πριν και μετά την χορήγηση αγωγής, σχετίστηκε σημαντικά με το Harvey-Bradshaw Index score (HBI). Επιπλέον η IL-24 βρέθηκε αυξημένη σε ασθενείς με ενεργό ΕΚ και ΝΚ μετά την θεραπεία και η έκφρασή της στην ΕΚ βρέθηκε να σχετίζεται σημαντικά με το Mayo σκορ. H IL-21 βρέθηκε αυξημένη στους ασθενείς με ΙΦΝΕ σε σχέση με τους υγιείς μάρτυρες χωρίς όμως να συσχετίζεται με την χορήγηση αγωγής ή με την ενεργότητα της νόσου. Η έκφραση της IL-33 διαπιστώθηκε αυξημένη μετά την χορήγηση αγωγής στους ασθενείς με ΕΚ και ΝΚ, προτείνοντας ότι δρα πιθανότατα προστατευτικά στον εντερικό βλεννογόνο. Ειδικότερα στην ΝΚ, τα επίπεδα έκφρασης της IL-33 σχετίστηκαν στατιστικά με την ενεργότητα της νόσου σύμφωνα με το HBI. H συγκεκριμένη μελέτη αποτελεί μία από τις πρώτες μελέτες σε ανθρώπους, σχετικά με την ανοσοϊστοχημική έκφραση των IL-21, IL-24, IL-19 και IL-33 στον εντερικό βλεννογόνο ασθενών με ΙΦΝΕ και καταδεικνύει την σημασία τους στην εντερική φλεγμονή, υποστηρίζοντας την μελλοντική χρήση τους ως θεραπευτικούς στόχους, διαγνωστικούς δείκτες ή ως βιοδείκτες ανταπόκρισης στην αγωγή με βιολογικούς παράγοντες.
Διαχείριση του στρες και του άγχους κατά τη μετάβαση στην εμμηνόπαυση
Authors: Παλαιολόγου Αναστασία
Published: October 2023

Εισαγωγή: Το στρες και η ψυχολογία μπορεί να επηρεάσουν τα κλιμακτηριακά συμπτώματα που βιώνουν οι γυναίκες κατά τη μετάβαση στην εμμηνόπαυση και αντίστοιχα τα κλιμακτηριακά συμπτώματα με τη σειρά τους, μπορεί να επηρεάσουν τα επίπεδα στρες. Σκοπός: Η παρούσα μελέτη στοχεύει στην αξιολόγηση της αποτελεσματικότητας ενός δομημένου προγράμματος διαχείρισης του στρες, που έχει σκοπό τη μείωση των συμπτωμάτων στρες, των κλιμακτηριακών συμπτωμάτων καθώς και τη βελτίωση του μεταβολικού προφίλ σε περιεμμηνοπαυσιακές και μετεμμηνοπαυσιακές Ελληνίδες γυναίκες. Υλικό και Μέθοδος: Στη μελέτη μας, συμπεριλήφθηκαν 103 περιεμμηνοπαυσιακές και μετεμμηνοπαυσιακές γυναίκες, ηλικίας 40-65 χρόνων με κλιμακτηριακά συμπτώματα και συμπτώματα στρες. Οι γυναίκες κατανεμήθηκαν τυχαία σε ομάδα παρέμβασης (51) και σε ομάδα ελέγχου (52). Και οι δύο ομάδες απάντησαν στο ίδιο ερωτηματολόγιο στην αρχή της μελέτης και υποβλήθηκαν σε βιοχημικές εξετάσεις για την εκτίμηση του μεταβολικού τους προφίλ. Μετά τις 8 εβδομάδες του προγράμματος διαχείρισης του στρες, το οποίο ακολουθήθηκε μόνο από την ομάδα παρέμβασης, οι δύο ομάδες συμπλήρωσαν εκ νέου το αρχικό ερωτηματολόγιο και έκαναν εκ νέου τις ίδιες βιοχημικές εξετάσεις. Ως εκ τούτου, αξιολογήθηκαν οι αλλαγές σε σχέση με τις αρχικές απαντήσεις. Αποτελέσματα: Η ομάδα παρέμβασης βελτιώθηκε σημαντικά σχεδόν σε όλες τις παραμέτρους συγκριτικά με τις αρχικές απαντήσεις. Η ένταση των αγγειοκινητικών συμπτωμάτων (-1.76±1.68, p-value < 0.001), τα συναίσθημα της ντροπής (-1.24±3.06, p-value 0.006), ενοχής (-1.37±3.63, p-value = 0.009), υπερηφάνειας (3.57±4.05, p-value < 0.001), ο έλεγχος του θυμού (3.04±4.56, p-value<0.001), η αυτοεκτίμηση (4.24±3.35, p-value<0.001), η αυτό-αποτελεσματικότητα (4.19±5.13, p-value <0.001), το αντιλαμβανόμενο στρες (-2.90±4.46, p-value <0.001), η κατάθλιψη (-2.16±3.11, p-value <0.001), το άγχος (-1.30±3.22, p-value = 0.006) το στρες (-2.90±4.46, p-value <0.001) και ο ύπνος (-1.45±2.58, p-value<0.001) ενώ στην ομάδα ελέγχου παρατηρήθηκε αλλαγή μόνο στην ένταση των αγγειοκινητικών συμπτωμάτων (0.19±0.65, p-value = 0.040) στα συναισθήματα ντροπής (-0.62±1.82, p-value = 0.018), ενοχής (-1.06±1.91, p-value < 0.001), στο στρες (-1.85±2.40, p-value <0.001) και στον ύπνο (-0.54±1.34, p-value = 0.005). Ανάμεσα στις δύο ομάδες παρατηρήσαμε μια σημαντική διαφορά στον έλεγχο θυμού (F = 41.786, p-value < 0.001, στο συναίσθημα υπερηφάνειας (F = 5.610, p-value = 0.020) και στο στρες (F = 33.594, p-value < 0.001). Τέλος, παρατηρήσαμε ότι η ταξινόμηση σε ομάδα παρέμβασης και ελέγχου δεν είχε σημαντική επίδραση στην επίπτωση του μεταβολικού συνδρόμου (F = 0.599, p-value = 0.441) αλλά η χρονο-εξαρτώμενη επίδραση του προγράμματος παρέμβασης είχε σημαντική επίδραση αλλαγής σχεδόν σε όλες τις παραμέτρους. Συμπεράσματα: Η διαχείριση του στρες μειώνει τα κλιμακτηριακά συμπτώματα και βελτιώνει την ποιότητα ζωής των μετεμμηνοπαυσιακών γυναικών χωρίς φαρμακολογική παρέμβαση.
Current trends in Greek puppet theatre.
Authors: Paroussi Antigoni , Lenakakis Antonis
Published: October 2023

When social and political upheavals are testing the art of puppetry, education, and most importantly, the relationship between theater and education, the digital edition of this volume aspires to present to the general public its "today". Greek puppetry, which is very different from the stereotypical image that circulates in much of the educational world. The volume aspires to capture, as much as possible, the dynamics of its existence and its history, a story that convinces that no matter how much it was underestimated as a theatrical genre, no matter how many exclusions it accepted, it is here and continues to entertain and "erode"» with its special characteristics both the fields of education and those of other arts.
A study of the biopsychosocial rehabilitation of patients with myocardial infarction six months after their discharge from the Cardiac Care Unit
Authors: Apostolopoulou Eleanna , Tsagri Charalampia , Kipourgos George , Tzenalis Anastasios
Published: October 2023

Background: Acute myocardial infarction is one of the leading causes of death in the developed world. The purpose of this research is to study the biopsychosocial rehabilitation of patients with myocardial infarction six months after their release from the heart attack unit.
Method and Material: The population of the study consisted of patients who had suffered a myocardial infarction and had been hospitalized in the heart attack unit of a University General Hospital six months ago. The study sample was 100 patients. The sampling method is simple randomization.
Results: Problems of anxiety and sadness with a percentage of 50% are in first place, followed by problems of pain and discomfort at a percentage of 24%, problems in performing usual daily activities at a percentage of 22%, mobility problems at a percentage of 16 % and finally the problems of self-care at a rate of 12%. There is a statistically significant difference between genders, with men being more affected with mobility problems (p-value= 0.014) and with performing usual activities (/p-value= 0.003). Patients who are ≤65 years of age appeared to be more affected compared to those >65 years of age in terms of mobility problems (/p-value= 0.009).
Conclusions: Quality of life improves for most patients after myocardial infarction. Whether or not patients have problems on one or more dimensions of the EQ-5D is highly related to the patient's profile. Fewest problems are observed in the self-care dimension and most problems are reported in the anxiety or sadness dimension.
Patient safety and quality of Health Care Provided
Authors: Kadda Olga
Published: October 2023

No abstract available
Protection and enhancement of the historical and architectural heritage in times of peace on apparently distant war wounds. Some cases in Cagliari (Italy) between restorations, current problems and future prospects
Authors: Dessi Maria , Fara Emanuela , Piredda Piervanna
Published: October 2023

The most recent conflicts in the European territory have focused the attention on the question of the protection of heritage after the war event, which now not appears in Italy as a distant problem, both temporally and geograph- ically. The study here proposed examines the case of the city of Cagliari, the regional capital of Sardinia (Italy), which is centrally located in the Mediterra- nean. The city appears to be an interesting and complete model due to the variety of cases that can be found here. It seems interesting how the typology of property has (or has not) often led to a reconstruction method.
Historical cartography and images was compared with the current state; it is pos- sible to observe the results of the buildings reconstruction (or part of the building) or urban void generated, to identify the main unsolved problems.The problems generated by the Second World War bombings, were examined eighty years after the end of the conflict. We therefore want to understand what the approach to reconstruction in relation to the different intended uses of the assets and their architectural quality was, in the various decades, from the post- war period until today.
Furthermore, it is interesting to examine whether the interventions were carried out in accordance with the regulations and / or with cultural indications that have followed, by comparing the local issue with the national one. This occasion ap- pears to be useful to reflect on the results of the damages of the city, where they remain severely compensable.
El “Historiae encomium” (1517) de Andrea Alciato: introducción, edición crítica y traducción anotada/The “Historiae encomium” (1517) by Andrea Alciato: introduction, critical edition and annotated translation
Authors: Antón Beatriz
Published: October 2023

Historiae encomium es el título con el que, desde 1530, se conoce la Epístola a Galeazzo Visconti que el jurista Andrea Alciato escribió como prefacio a sus Annotationes in Cornelium Tacitum (Milán, 1517). En este texto no solo hace un entusiasta elogio de la historia, que considera superior a otras disciplinas, sino una vehemente defensa de Tácito, al que concede la primacía sobre Tito Livio. Sin embargo, no existe aún una edición moderna ni una traducción de dicha Epístola. De ahí mi intención de hacer la primera edición crítica del texto latino y la primera traducción completa y anotada, a fin de facilitar la comprensión de un opúsculo con el que Alciato marcó un hito en la pervivencia de Tácito y en la corriente tacitista.
Tácito, Saavedra, y la “Censura sobre los Anales de Tácito (Ms. 13086)”/Tacitus, Saavedra, and The “Censorship on The Annals of Tacitus (Ms. 13086)”
Authors: Cid Vázquez María Teresa
Published: October 2023

Se reflexiona sobre la posible autoría del documento que se conserva en la Biblioteca Nacional de Madrid, “Censura sobre los Anales de Tácito…”, ms. 13086. El colector de la miscelánea lo catalogó como anónimo a pesar del nombre que figura en una hoja adjunta al documento: Pedro Ponce de León. En este artículo se plantea una hipótesis sobre su posible autoría: Pedro Ponce de León podría ser el seudónimo con el que ocultó su identidad don Diego de Saavedra Fajardo.
Tácito en la revolución americana
Authors: Martinez Maza Clelia
Published: October 2023

Tácito fue uno de los escritores más reconocidos en los círculos intelectuales de la América revolucionaria. No se conservan muchas referencias explícitas en los escritos del periodo, pero su influencia es perceptible en los argumentos empleados para legitimarla independencia de las colonias del Imperio británico. En el siguiente trabajo, se identificarán los elementos de la obra de Tácito que fueron recuperados por los padres fundadores durante la revolución. Las traducciones consultadas de clara ideología whig, modelaron la interpretación de la obra de Tácito y su aplicación en la práctica política. Además, se analizará su empleo en el debate político de formas bien distintas, pero siempre por su utilidad en la construcción de la nueva república.
Mediation: resolving disputes with employees
Authors: Bernstein Adam
Published: October 2023

Adam Bernstein discusses the role of mediation in disputes between employees and employers
Division and the Digital Language Divide: A Critical Perspective on Natural Language Processing Resources for the South and North Korean Languages
Authors: Berthelier Benoit
Published: October 2023

Abstract: The digital world is marked by large asymmetries in the volume of content available between different languages. As a direct corollary, this inequality also exists, amplified, in the number of resources (labeled and unlabeled datasets, pretrained models, academic research) available for the computational analysis of these languages or what is generally called natural language processing (NLP). NLP literature divides languages between high- and low-resource languages. Thanks to early private and public investment in the field, the Korean language is generally considered to be a high-resource language. Yet, the good fortunes of Korean in the age of machine learning obscure the divided state of the language, as recensions of available resources and research solely focus on the standard language of South Korea, thus making it the sole representant of an otherwise diverse linguistic family that includes the Northern standard language as well as regional and diasporic dialects. This paper shows that the resources developed for the South Korean language do not necessarily transfer to the North Korean language. However, it also argues that this does not make North Korean a low-resource language. On one hand, South Korean resources can be augmented with North Korean data to achieve better performance. On the other, North Korean has more resources than commonly assumed. Retracing the long history of NLP research in North Korea, the paper shows that a large number of datasets and research exists for the North Korean language even if they are not easily available. The paper concludes by exploring the possibility of "unified" language models and underscoring the need for active NLP research collaboration across the Korean peninsula.
Motivations for the Creation of Social Justice Guides: A Survey of ARL Member Institutions
Authors: Piper Gemmicka , Ameen Mahasin , Lowe M. Sara
Published: October 2023

abstract: This study surveyed librarians and staff at Association of Research Libraries (ARL) member institutions to determine who assembles social justice guides (that is, LibGuides), what motivated the creation of such guides, and how these guides are deployed. Additionally, the survey gauged employee perceptions of library and institutional responses to social unrest. Sociopolitical events, perceived educational need, and work assignments to develop such a guide were the primary reasons motivating the creation of the guides. Social justice guides are seldom incorporated or deployed into wider library or institutional programming, however. Overall, library and institutional diversity statements and responses to social unrest were perceived as words without action. Results from this survey shed light on library employee perceptions, on the emotional labor involved in the development of anti-racist resources, and on library and institutional responses to social unrest.
Addressing Classification System Bias in Higher Education Libraries in England
Authors: Smith Trista , Appleton Leo
Published: October 2023

abstract: This qualitative research study explores the ways that academic librarians in England undertake and perceive classification and cataloging work to engage in wider decolonization initiatives. The research consisted of semi-structured interviews, and thematic analysis was used to identify key themes. The study found that the participant librarians highly value this work based on a perception of its moral importance, rather than concrete proof of impact. Benefits from a decolonization perspective were not always clear. Challenges include staffing shortages and technological limitations.
Requesting Librarian-Led Information Literacy Support: Instructor Approaches, Experiences, and Attitudes
Authors: Stonebraker Ilana , LeMire Sarah
Published: October 2023

abstract: This project sought to better understand why course instructors request librarian involvement to teach information literacy skills. Librarians at two large institutions surveyed 29 instructors and then interviewed 11 about their experiences working with librarians, their motivations for involving librarians in their courses, and their goals for including information literacy instruction. The study found that instructors had many different levels of experience with the library. Motivations for inviting librarians to their classes included creating a support network and sharing librarian expertise with students. The researchers also discuss instructor participation in library instruction sessions, including commentary, where they reinforce points made by the librarian during class, and bookending, where they sandwich librarian involvement between preliminary or concluding remarks.
Calibrating Costs: Do Tuition Reset Policies Affect Diverse Student Enrollment at Private Baccalaureate Colleges?
Authors: Corral Daniel , Ward James
Published: October 2023

This study focuses on tuition reset policies, where colleges reduce the
published sticker price by at least 5%, and in many instances, much more. We
use a difference-in-differences design to examine the effect of these policies on
student enrollment disaggregated by race/ethnicity and a proxy for economic
disadvantage. On average, these policies do little to move the needle regarding
specific racial/ethnic diversity on campus; however, we find that these institutions
experience a 6.5% increase in the share of Pell Grant students following
the introduction of these policies.