bluuebunny/crossref_metadata_2025_split huggingface dataset:
THU297 Metformin Treatment Of Juvenile Mice Alters Aging-Related Developmental And Metabolic Phenotypes In Sex-Dependent And -Independent Manners
Authors: Zhu Yun , Engmann Morgan , Medina David , Bartke Andrzej , Ellsworth Buffy S , Yuan Rong 
Published: October 2023

Abstract
Disclosure: Y. Zhu: None. M. Engmann: None. D. Medina: None. A. Bartke: None. B.S. Ellsworth: None. R. Yuan: None.
Metformin is a widely used drug for the treatment of type 2 diabetes that also has a strong potential for long-term effects which may extend healthspan and longevity. In the current study, C57BL/6J (B6) juvenile female and male mice were treated with metformin between the ages of 15 and 56 days. Saline was used as the control. The results show that early-life treatment with metformin has profound effects on developmental and metabolic traits. Body weight was significantly reduced by metformin treatment in both sexes (P&lt;0.05, t test). At 10 weeks of age, mice were euthanized, and organ weights were recorded. In treated males, weights of epididymal, perirenal, and brown fat depots were significantly reduced (P&lt;0.05, t test). Pancreas weight was significantly reduced in both sexes (P&lt;0.05, t test). Hypothalamus weight was significantly reduced in the females, and whole brain weight was significantly reduced in the males. Tail length as well as age of sexual maturation were not significantly altered in either sex. No significant difference was found in circulating insulin-like growth factor 1 (IGF1) or adiponectin. Circulating insulin was significantly reduced by the treatment under fasting and non-fasting conditions in the male mice, while in the females no significant difference was detected. Insulin sensitivity, calculated by the quantitative insulin-sensitivity check index (QUICKI), was suggestively increased in the male mice (P=0.062, t test). Glucose tolerance test (GTT) did not show a significant difference in treated female mice; however, comparing the area under curve, metformin treatment significantly improved the glucose tolerance of male mice (P=0.014, t test). Insulin tolerance test (ITT) showed no significant difference in the male mice; but, unexpectedly, in female mice, metformin treatment significantly reduced insulin sensitivity. This study revealed that early-life metformin treatment alters development and metabolism of mice in both sex-specific and non-specific manners, which may have long-term impacts on metabolism in aging. Interestingly, comparing the results of this study with previous studies of metformin-treated heterogenous UM-HET3 mice, further analyses revealed that metformin effects on body weight, age of sexual maturation, body size, IGF1, adiponectin, insulin, GTT, and ITT, are genetically dependent.
Funding: SIU collaborative grant to Rong Yuan and Buffy S. Ellsworth. SIU Geriatric foundation by Andrzej Bartke
Presentation: Thursday, June 15, 2023
FRI662 Quetiapine Induced Severe Hypoglycemia In Elderly Patients Without Diabetes
Authors: gusov timur , Akofu Anota , marium fnu , Dejhansathit Siroj , Gardner Michael J , Sheung Nicole , Uddin Ashraf , Akabogu Nwamaka 
Published: October 2023

Abstract
Disclosure: T. gusov: None. A. Akofu: None. F. marium: None. S. Dejhansathit: None. M.J. Gardner: None. N. Sheung: None. A. Uddin: None. N. Akabogu: None.
Introduction: Quetiapine is a second-generation antipsychotic (SGA) commonly used for a wide range of psychotic and mood disorders, sleep aid and others. Older individuals are often treated with quetiapine to relieve psychotic symptoms associated with conditions including dementia and delirium. Common metabolic side effects include weight gain, hyperglycemia, dyslipidemia, and diabetes mellitus. There are few reports of mild asymptomatic hypoglycemia in individuals without diabetes. Hypoglycemia is a serious medical condition with high morbidity and mortality. We report an older individual without diabetes who developed severe hypoglycemia from treatment with quetiapine. Clinical case: 84 years old female was admitted to the hospital for altered mentation, right sided weakness. Cerebral vascular accident was ruled out with imaging studies. The patient was found to be hypoglycemic at 64 mg/dl. Treated with IV D5 with effect, hypoglycemia recurred and was persistent, IV treatment with glucose was initiated. Laboratory results: glucose 46 mg/dL, C- peptide 0.361nmol/L, insulin 1.21 mcunit/ml, proinsulin 6.1 pmol/L, sulfonylurea negative, beta hydroxybutyrate 0.97mmol/L, insulin Ab negative, Administration of 1 mg of glucagon increased blood glucose by 20 mg/dl. Cosyntropin test was normal, TSH and thyroxine levels are normal. Abdominal US ruled out obvious liver and pancreatic pathology. Medication list reviewed. Quetiapine was suspected as the cause and was stopped. Within the next 24 hours blood glucose normalized, IV glucose treatment stopped. She was observed for 2 more days, had no recurrent episodes and was discharged. Conclusion: Quetiapine is widely used to relieve psychotic symptoms and sleep aid. MEdication is usually associated with hyperglycemia. In the present case we report quetiapine-induced hypoglycemia in the patient without diabetes, which was more severe than that described in previous reports, and required dextrose fluid infusion. Quetiapine may increase the amount of basal insulin secreted by pancreatic β-cells and thereby cause hypoglycemia. Since quetiapine is used for the relief of psychotic symptoms, it is crucial to understand the potential adverse effects related to the use of this medication, and to observe any symptoms that may appear. We suggest that clinicians should carefully observe older patients receiving quetiapine to identify any hypoglycemic symptoms that may appear. Reference: Quetiapine-Induced Severe Hypoglycemia in the patient without Diabetes Mellitus: A Case Report Suk Ju Cho, Sang Ah Lee. Annals of Geriatric Medicine and Research 2019;23(1):35-37
Presentation: Friday, June 16, 2023
OR12-01 Blocking The Maladaptive Integrated Stress Response Increases Immunosuppressive PD-L1 In Pancreatic β-Cells
Authors: Muralidharan Charanya , Huiping huang Fei , May Sarah C , Enriquez Jacob , Nelson Jennifer B , Wang Eugenia , Chakraborthy Advaita , Figatner Kayla T , Navitskaya Svetlana N , Tersey Sarah A , Mirmira Raghavendra G 
Published: October 2023

Abstract
Disclosure: C. Muralidharan: None. F.H. huang: None. S.C. May: None. J. Enriquez: None. J.B. Nelson: None. E. Wang: None. A. Chakraborthy: None. K.T. Figatner: None. S.N. Navitskaya: None. S.A. Tersey: None. R.G. Mirmira: None.
In type 1 diabetes (T1D), the immune system destroys the insulin-secreting β-cells. This autoimmune attack may be triggered by the β-cells themselves when they encounter viral infections or changes in gut microbiome or diet, years before clinical diagnosis of T1D. In response to these stressors, four kinases (PERK, PKR, GCN2, and HRI) activate the integrated stress response (ISR), which temporarily halts protein translation to promote cellular survival. However, if prolonged, the ISR can render β-cells dysfunctional. Therefore, we hypothesized that inhibiting the ISR under chronic inflammatory stress would suppress β-cell autoimmunity and reduce T1D risk. To test this, we pre-treated human islets with ISR inhibitors (ISRIB or a novel inhibitor of PERK, HC-PERKi) and then exposed them to proinflammatory cytokines (50 IU/mL IL-1β + 1000 IU/mL IFNγ) for 24h. As expected, cytokine treatment blocked protein translation, as revealed by polyribosomal profiling. Consistent with this, we saw reduced total protein synthesis (50% decrease) by puromycin incorporation assay. These effects were partially reversed by pretreating with ISR inhibitors. To determine if ISR inhibition delays or prevents diabetes development, we treated female pre-diabetic non-obese diabetic (NOD) mice with vehicle or HC-PERKi for four weeks (6-10 weeks of age). Compared to controls, NOD mice that received HC-PERKi showed a significant delay in diabetes development. Single cell RNA-sequencing analysis of the pancreatic islets revealed alterations in pathways involved in antigen processing and presentation in the β-cell clusters of HC-PERKi islets. Consistent with this observation, spatial proteomics analysis of the pancreatic β-cell area of HC-PERKi islets revealed a striking upregulation of programmed death-ligand 1 (PD-L1), an immune checkpoint regulator that suppresses adaptive T-cell immunity. Notably, there was no change in transcript levels of PD-L1, suggesting that PD-L1 levels are post-translationally regulated. Collectively, our studies show that inhibition of the ISR activates general protein synthesis, reduces immunogenicity via increased β-cell PD-L1 levels, and decreases T1D risk. Whereas the ISR is an adaptive response, our work emphasizes how the ISR could become maladaptive under chronic inflammation and promote β-cell autoimmunity.
Presentation: Friday, June 16, 2023
OR18-01 Massively Parallel Functional Assay Of Extracellular Insulin Receptor Variants
Authors: Aslanzadeh Vahid , Brierley Gemma , Kudla Grzegorz , Kenneth Semple Robert 
Published: October 2023

Abstract
Disclosure: V. Aslanzadeh: None. G. Brierley: None. G. Kudla: None. R.K. Semple: None.
Loss-of-function mutations in the gene for the human insulin receptor, INSR, cause either autosomal dominant or autosomal recessive severe insulin resistance. Biallelic mutations produce extreme insulin resistance which is commonly fatal in infancy or childhood. A wide and growing number of mutations have been associated with disease, with few recurring mutations, and only a small subset have been studied functionally to date. Discriminating loss-of-function pathogenic alleles from insignificant variants is an important barrier to diagnosis and translational studies of novel candidate treatments. Such candidate therapies include a variety of antibody, peptide and small molecule ligands that activate the receptor in a manner distinct to insulin. These show potential to activate mutant receptors that are expressed but show impaired insulin binding or responsiveness. To address this barrier to translation we have now used massively multiplexed, Flow-Seq-based assays simultaneously to determine the effects of 14,000 human INSR extracellular domain missense variants. We assayed receptor cell surface expression, insulin binding and signal transduction using heterologous expression of mutants in mouse embryonic cells in which endogenous Insr and Igf1r genes had been knocked out or knocked down. Preliminary analysis reliably discriminates A. variants that reduce or abolish receptor cell surface expression when measured with two different monoclonal anti-receptor antibodies B. variants with preserved cell surface expression but selectively impaired binding of insulin and C. an overlapping group of variants with severely impaired signalling response to insulin but preserved response to antibody. Our assay confirmed previously studied attributes of a panel of disease-causing variants, and shows strong agreement with prior alanine scanning mutagenesis studies and structural predictions. We thus provide a rich sequence-function map for INSR variant interpretation. A prediction tool trained on known pathogenic INSR alleles is currently being developed for access by the community both to accelerate confident molecular diagnosis of newly identified rare INSR variants, and also to aid stratification of mutations according to potential for activation by non canonical INSR ligands.
Presentation: Saturday, June 17, 2023
SAT034 Exploring The Role Of Zfp664 In Hepatic Glucose Regulation
Authors: Tsay Ariel , Wang Jen-Chywan 
Published: October 2023

Abstract
Disclosure: A. Tsay: None. J. Wang: None.
Genome wide association studies (GWAS) identify the association between variants at genomic loci and common diseases. These variants consist of single nucleotide polymorphisms (SNPs), which can be localized within coding or non-coding regions. The former could affect the functions of proteins encoded by these genes. The latter could modulate the expression of genes contained or localized nearby these SNPs. Several SNPs associated with metabolic disease such as diabetes, obesity, and dyslipidemia are found in and nearby the human ZNF664 gene, which encodes a zinc finger protein that is predicted to be a transcriptional regulator. The mouse homolog of ZNF664 is Zfp664, whose amino acid sequence is identical to ZNF664. To learn whether Zfp664 contains a transcriptional activation or repression function, the expression plasmid harboring the cDNA of full length or deletion mutants of mouse Zfp664 fused to yeast GAL4 DNA binding domain (DBD) was transfected into HEK293T cells along with a luciferase reporter plasmid containing 5 copies of the GAL4 binding sites. We saw decreased luciferase activity in cells overexpressing the GAL4 DBD and full length Zfp664 fusion protein. Thus, Zfp664 acts as a transcriptional repressor. The deletion analysis identified that amino acid 7 to 95 of Zfp664 was required for its transcriptional repressive activity. To test the metabolic function of hepatic Zfp664, 8 weeks old male C57Bl/6J mice were infected with adeno-associated virus (AAV) expressing either scramble small hairpin RNA (shRNA, as a control) or shRNA targeting Zfp664 and then fed a normal chow diet or western diet (42% kcal from fat, 0.2% total cholesterol) for 12 weeks. We found that mice infected with AAV expressing Zfp664 shRNA had a lower expression of Zfp664 in the liver but not in epididymal white adipose tissue and gastrocnemius muscle. Under chow diet feeding, not only did hepatic Zfp664 knockdown not affect glucose tolerance and insulin sensitivity, but it also did not affect fasting glucose, insulin, triglyceride, and total cholesterol levels. In contrast, in mice fed a western diet, hepatic Zfp664 knockdown worsened glucose tolerance and elevated fasting insulin levels. Moreover, the expression of hepatic gluconeogenic genes, such as phosphoenolpyruvate carboxykinase (Pck1) and the catalytic subunit of glucose-6-phosphatase (G6pc), was increased. The fasting plasma triglyceride and total cholesterol levels were not affected by hepatic Zfp664 knockdown in western diet fed mice. Overall, these results discover the novel role of Zfp664 in the regulation of hepatic glucose homeostasis.
Presentation: Saturday, June 17, 2023
Assessment of the Current State of Sports Coverage Participation, Training, and Confidence Ratings among Physical Medicine and Rehabilitation Residents and Residency Programs
Authors: Stokes Derek , Heronemus Marc , Cali Malia , Meron Adele , Laker Scott R. 
Published: October 2023

AbstractA significant proportion of physical medicine and rehabilitation residents are pursuing sports medicine-related fellowships and are recommended to participate in sports coverage during residency training. The purpose of this article is to assess the current state of sports coverage participation, training, and confidence ratings among physical medicine and rehabilitation residents and residency programs. Physical medicine and rehabilitation residents from Accreditation Council for Graduate Medical Education-accredited programs were invited to participate in a nationwide cross-sectional survey. A total of 90 resident responses from 43 programs were included. Residents from 91% of represented programs indicated that sports coverage opportunities were available. At least one resident from 63% of represented programs and 50% of responding residents reported sports coverage training during residency. Sports coverage confidence ratings were higher in 91% of topics among residents who received training. The results of this study indicate that sports coverage opportunities are common among physical medicine and rehabilitation residencies, and while sports coverage training is variable, a positive correlation with confidence ratings was identified.
RETRACTED: Ameliorative effect of gel combination of Centella asiatica extract transfersomes and rosemary essential oil nanoemulsion against UVB-induced skin aging in Balb/c mice [version 1; peer review: 3 approved with reservations]
Authors: AlOmran Abdullah , Dewi Lestari Ismail Dina , Widasmara Dhelya , Riawan Wibi , Retnaningtyas Ekowati , Weka Nugraheni Raditya , Eka Puspita Oktavia , Rahayu Adianingsih Oktavia , Mardiyah Mardiyah , Setiawan Andri 
Published: October 2023

RETRACTION NOTICE (3rd October 2023): The article by Khotimah H, Dewi Lestari Ismail D, Widasmara D et al. ‘Ameliorative effect of gel combination of Centella asiatica extract transfersomes and rosemary essential oil nanoemulsion against UVB-induced skin aging in Balb/c mice’[version 1; peer review: 3 approved with reservations] (https://doi.org/10.12688/f1000research.109318.1) has been retracted from F1000Research by the F1000 Editorial Team. During prepublication checks of a new article by these authors, the F1000 Editorial Team noticed that the dataset and methodology of the new article were very similar to this published article. Investigation into the content of these two articles was performed by the F1000 Editorial Team, which revealed discrepancies in the ethical approval (approval document mentioned rats when the study was in mice; new article mentioned consent when study in animals) and methodology (wrong description of mouse model used); and concerns over the treatment of the mice (wellbeing concerns during shaving procedure and euthanasia) and authenticity of the data. The new article was rejected. For this published article, the F1000 Editorial Team requested an explanation from the authors regarding the above issues, including a request for a copy of the ethical approval document, on 22nd March and 29th March 2023. The authors’ institution was contacted on 24th April and 21st June 2023. The authors were unable to respond adequately to our queries; the institution has not responded to our requests. The decision was made by the F1000 Editorial Team to retract this article, due to the inability to verify the ethical approval for this study, and concerns over data integrity and the study design, including the treatment of the mice. The authors have seen a copy of this retraction notice. Husnul Khotimah and Dina Dewi Lestari Ismail agree with the retraction of the article. No responses were received from the other authors.
The role of newspapers published in North Sumatra during Indonesia's independence struggle between 1916-1925: A content analysis
Authors: Azhari Ichwan , Sidiq Ricu , Purnamasari Ika 
Published: October 2023

Background: Newspapers played an important role in fostering a sense of nationalism, instilling the concept of "nation", fostering a sense of belonging, and maintaining the unity that the colonized people desperately needed to achieve independence. This study aims to investigate the involvement of indigenous newspapers in the struggle for Indonesian independence in North Sumatra during the Dutch colonial period, as well as to highlight how the contents of the newspaper's coverage were narrated in the struggle for Indonesian independence. Methods: This study used a qualitative content analysis (QCA) method. Research analysis includes manifest analysis (shown on the surface of the text) and latent analysis (hidden in the text) on the title, topic and sentence of each article. The validity test was carried out by peer-reviewing coding books and coding forms. Reliability test in the form of Intercoder reliability using NVivo 12 interrater reliability. Results: The results of the study found 107 articles in 13 indigenous newspapers in North Sumatra that supported the struggle for Indonesian independence from Dutch colonialism. There are 7 forms of narrative of the struggle for Indonesian independence in indigenous newspapers in North Sumatra from 1916-1925. The seven narratives are found in the title, topic, and sentences written in the article. National movements were the most narratives found with 36.73% found in titles (N= 49), 26.09% in topics (N=89), and 23.72% in sentences in the text (N=156). The fewest narrations were criticisms and demands to the Netherlands of 2.04% for title analysis. The next least narrative is patriotism with a score of 5.43% for topic analysis and 6.41% for sentences in the text. Conclusion: The role of newspapers in the struggle for independence in North Sumatra is evidenced by the findings of 107 articles in 13 newspapers in seven forms of struggle narratives.
Meeting the Moment: Socially Engaged Performance, 1965–2020, by Those Who Lived It, Jan Cohen-Cruz and Rad Pereira (2022)
Authors: Salgado Mauricio Tafur 
Published: October 2023

Review of: Meeting the Moment: Socially Engaged Performance, 1965–2020, by Those who Lived it, Jan Cohen-Cruz and Rad Pereira (2022)
New York: New Village Press, 274 pp.,
ISBN 978-1-61332-154-6, p/bk, $26.95
Intercultural Dramatherapy: Imagination and Action at the Intersections of Difference, Ditty Dokter and Nisha Sajnani (2023)
Authors: Luckwaldt Robin , Bleuer Jessica 
Published: October 2023

Review of: Intercultural Dramatherapy: Imagination and Action at the Intersections of Difference, Ditty Dokter and Nisha Sajnani (2023)
New York: Routledge, 288 pp.,
ISBN 978-1-138363-347-2, h/bk, $160.00
ISBN 978-1-13836-348-9, p/bk, $39.95
ISBN 978-0-42943-159-3, e-book, $35.95
Exploring Achievement Behaviors in Non-Major Statistics Course: An Expectancy-Value Perspective and Thoughts for Practice
Authors: Smith Tamarah , Dai Ting 
Published: October 2023

Statistics education is increasingly important to our society with enrolment increases of 16% in introductory statistics courses and 85% in upper-level statistics courses. Research has demonstrated many factors related to students’ behaviors and outcomes in statistics courses such as past achievement, attitudes, and effort. We sought to model these factors together to better understand how introductory statistics students’ attitudes were related to students' achievement behaviors and what student characteristics mediated such relationships. Structural equation modeling with data from N=301 students in an introductory statistics course for psychology majors revealed that majors with higher GPAs had more interest, enjoyment as well as utility value for statistics, and these variables were in turn related to expectations for success or achievement behaviors. Females had lower interest in statistics, and this was related to lower expectations of success. The findings highlight the need to increase interest and enjoyment and utility value for non-majors studying statistics. Recommendations for how to adapt the statistics classroom to that end are discussed.
Reading and writing in n-dimensional face space
Authors: Forzano Silvia Barbotto 
Published: October 2023

Abstract
This manuscript begins with a brief introduction that establishes the theoretical background, followed by a tripartite unfolding that explains the following contents: 1) the path from point zero as a plurimorphic space of semiotic tranquility; 2) the historical trajectory of physiognomy and pathognomy suggestions; and 3) new biometric readings and the digital face. We postulate the neutral state of the face and see a possible manifestation of it in the tranquility illustration and theorization by Le Brun. Together with the passive face recounted by Magli, these are some of the static aspects of that space called the face, full of signs that write and compose it and allow its physiognomic reading. Degree zero, the pre-signal null point from which interpretation originates, determines the semiotic potential of the face, and the expressions of the emotions become the key to pathognomy studies, in their historical-cultural variants. We will then see how, in today’s highly technological and mediatized society, there are new biometric manifestations linked to the digital face. From the Bertillonage of the early 1900s, we conclude with a work of contemporary art that critically revisits the same approach.