bluuebunny/crossref_metadata_2025_split huggingface dataset:
Yy1 Depletion in Pancreatic Beta Cells Leads to Energy Source Switch From Glycolysis to Oxidative Phosphorylation
Authors: Perez-Garcia Eliana M , Liu Ruya , Yechoor Vijay K 
Published: May 2021

Abstract
Background: Gene expression is determined by structural interactions in between transcription factors, cofactors and enhancer elements, as well as enhancer-promoter interactions (1). Both YY1 and CTCF are essential, zinc finger proteins that bind hypo-methylated DNA sequences, form homodimers, and thus facilitate DNA loop formation (1). ​However, YY1 preferentially occupies interacting enhancers and promoters, whereas CTCF preferentially occupies sites distal from these regulatory elements, forming larger loops and participating in insulation (1). A sequencing study of spontaneous functional insulinomas in a Chinese cohort identified a somatic a hotspot mutation in YY1 (c.C1115G/p.T372R) in 30% of the cases, associated with increased YY1 activity (2). YY1 is a critical transcription factor involved in the regulation of proliferation and metabolism (2).
Hypothesis: YY1 loss-of-function alters energy source preference in pancreatic β-cells.
Methods: YY1 stable loss-of-function in mouse insulinoma cell lines was achieved by shRNA lentiviral transduction. Mitochondrial membrane potential (MMP) was measured via flow cytometry of aggregated mitochondria to monomeric mitochondria ratio. Mitostress and complex-substrate controlled respiration were measured by Seahorse analyzer. Mitochondrial copy number was assessed by mitochondrial to nuclear DNA ratio. Quantitative qPCR and Western blotting were used to assess mitochondrial gene and protein expression.
Results: Our data indicated that YY1 deficient β-cells showed increased MMP and maximal respiration. No significant differences were found in basal respiration, ATP production, proton leak, non-mitochondrial oxygen consumption or coupling efficiency. We also found that YY1 deficient β-cells exhibited reduced glycolytic capacity and decreased ETC complex IV activity, with concurrent increased complex I and II activity. In addition, YY1 deficient β-cells exhibited elevated mitochondrial copy number​ and increased quantitative mRNA of mitochondrial gene expression, which could be correlated with increased PGC1-α expression.
Conclusions: YY1 is critical in the metabolic regulation of β-cells, particularly in the facilitation of glycolytic metabolism. YY1 activating mutations in functional spontaneous insulinoma cells can lead to a proliferation dysregulation accompanied by a metabolic switch that favors glycolysis, while the opposite occurs in YY1 deficient β-cells.
References: (1) Weintraub AS et al, Cell 2017 Dec 14; 171:1573–1588 (2) Cao Y et al, Nat Commun 2013 Dec 10; 4:2810
Clinical Effectiveness of a Protocol to Manage Deamthasone-Induced Hyperglycemia Among Hospitalized Patients With COVID-19
Authors: Asiri Alanood Ahmed , AlGuwaihes Abdullah , Jammah Anwar Ali , Alfadda Assim Abdulaziz , Al-Sofiani Mohammed E 
Published: May 2021

Abstract
Importance: Well-controlled glucose levels during hospitalization (i.e. 70–180 mg/dl) have been associated with lower mortality in patients with COVID-19. The recent addition of dexamethasone to COVID-19 treatment protocols has raised concerns about the negative metabolic consequences of dexamethasone including hyperglycemia. We developed a simplified, yet comprehensive, protocol to guide the management of dexamethasone-induced hyperglycemia in hospitalized patients with COVID-19.
Objectives: To present our protocol for the management of dexamethasone-induced hyperglycemia and examine its clinical effectiveness in the real world.
Methods: An algorithm-based protocol that outlines all aspects of the inpatient management of dexamethasone-induced hyperglycemia in COVID-19 patients, from time of admission to discharge including guidance on insulin titration, was disseminated to the COVID-19 teams in our hospital. Medical records of 163 patients admitted between June and September, 2020 who tested positive for COVID-19 and developed dexamethasone-induced hyperglycemia were reviewed. Fasting, pre-lunch, pre-dinner and bedtime glucose levels during the first five days of admission and day of discharge were compared between the 47 patients who were managed “Pre-Protocol” implementation and the 116 patients who were managed “Post-Protocol” implementation.
Results: On admission, there were no significant differences in age, proportion of women, BMI, prevalence of diabetes, and Charlson score between the “Pre-Protocol” and “Post-Protocol” groups (56 vs 56 years old, 30 vs 32% women, 28 vs 29 kg/m2, 45 vs 35% with diabetes, and 2 vs 2 median Charlson scores; respectively, all p&gt;0.05). The “Post-Protocol” group had higher proportions of patients with well-controlled glucose (i.e. 70–180 mg/dL) compared to the “Pre-Protocol” group, across all pre-meals and bedtime glucose readings throughout the hospital stay. The differences between the “Post-Protocol” and “Pre-Protocol” groups were statistically significant (p&lt;0.05) for fasting glucose on day 4, 5, and discharge day; pre-lunch glucose on discharge day; pre-dinner glucose on day 3, 5, and discharge day; and bedtime glucose on day 1. In regression analyses adjusted for age, sex, nationality, BMI, Charlson score, and diabetes status, the odds ratios of having well-controlled glucose were significantly higher in the “Post-Protocol” group versus the “Pre-Protocol” group for fasting glucose on day 4, 5, and on discharge; pre-lunch glucose on day 5 and on discharge day; pre-dinner glucose on day 3 and 5; and bedtime glucose on day 1.
Conclusion: The implementation of a simplified protocol for the management of dexamethasone-induced hyperglycemia in hospitalized patients with COVID-19 results in more patients achieving well-controlled glucose levels that have been previously associated with lower mortality of COVID-19.
Complications and Outcomes in Patients With Diabetic Ketoacidosis and COVID19
Authors: Hwang Patricia , Vellanki Priyathama , Galindo Rodolfo Javier , Brechtelsbauer Erika , Van Prooyen Amanda , Ashraf Shanza 
Published: May 2021

Abstract
Introduction: COVID-19 infection caused by the novel coronavirus SARS-CoV-2 has been associated with new-onset diabetes and diabetic ketoacidosis. There are currently limited reports observing the effect of COVID-19 infection on outcomes in patients hospitalized with diabetic ketoacidosis (DKA). Methods: This retrospective study used electronic medical records, between March 1, 2020 to September 14, 2020, and included patients aged ≥ 18 years with DKA. Clinical characteristics, hospital course, and complications (ICD-10 codes) were compared between patients admitted with DKA and confirmed COVID-19 infection (COVID+) to those with DKA without COVID-19 infection (COVID-). The American Diabetes Association criteria was used to define DKA. Results: Among 757 patients with DKA, 80 COVID+ patients with and 677 COVID- patients were included (mean age 49.1 years, female 52.7%, African-American 70.4%). Baseline characteristics were similar between groups. The COVID+ group had a lower admission glucose (mean glucose 413.1 ± 218.7 mg/dL vs 441.1 ± 222.6 mg/dL, p-value 0.05), and higher serum bicarbonate levels (18.2 mmol/L vs 16.6 mmol/L, p-value &lt;0.05) compared to the COVID- group. Compared to the COVID- group, COVID+ required a longer time to achieve blood glucose &lt; 250 mg/dl from admission (8.8 hours vs 7.1 hours, p-value &lt;0.01), and had higher rates of acute respiratory failure (48.8% vs 9.5%, p-value &lt;0.001), mechanical ventilation (32.5% vs 10.9%, p-value &lt;0.001), sepsis (37.5% vs 15.7%, p-value &lt;0.001), acute thrombotic events (11.3% vs 2.7%, p-value &lt;0.05), and pneumonia (70% vs 10.3%, p-value &lt;0.001). COVID+ had higher mortality (16.3% vs 3.1%, p-value &lt; 0.001), ICU length of stay (median 5.5 days or 2–58 days vs median 2 days or 2–123 days, p-value &lt;0.001), and total LOS (median 7.5 or 1–47 days vs median 5 days or 1–98 days, p-value &lt;0.001). Both groups required similar total insulin doses throughout the entire hospitalization (mean 143 +/- (SD) vs 142 +/- SD units, p-value 0.088). Conclusion: Our data shows that COVID-19 infection is associated with increased mortality, worse clinical outcomes, and longer LOS among patients hospitalized with DKA, while presenting with less severe hyperglycemia and acidemia compared to those without COVID-19 infection.
Endocrine Elective Primer for Medical Students
Authors: Bassin Sandhya , Lubitz Sara E 
Published: May 2021

Abstract
Background: Endocrine modules available online have shown improvement in student learning and increased student satisfaction with self-guided learning (Kirk, 2016). However, most available modules are geared towards preclinical medical students rather than clinical students. Therefore, we developed an endocrine primer, defined as a set of introductory preparatory material, in the form of a PowerPoint. The primer reviews commonly seen endocrine disorders in adults, including their presentation, diagnosis, and management, in order to offer students access to self-paced learning and help bridge the gap between the basic science curriculum and clinical experience.
Methods: Third and fourth year medical students enrolled in the endocrine elective from Feb 2020-Oct 2020 completed a 15 question pre-and post-knowledge assessment, as well as an endocrine primer satisfaction survey. The knowledge assessments evaluated students’ knowledge of topics surrounding type 1 and 2 diabetes, hyper- and hypothyroidism, thyroid nodules, adrenal and pituitary disease, hyperparathyroidism, and osteoporosis. The pre-knowledge assessment was completed prior to starting the endocrine elective and viewing the endocrine primer. The post-knowledge assessment was completed at the end of the two or four week endocrine elective.
Results: A paired-T test was used to compare the pre- and post-knowledge survey results. A total of 7 third- and fourth-year medical students completed the knowledge assessment and satisfaction survey. Knowledge results showed a nonsignificant mean improvement of 1.4 points, p=0.09, from the start of the elective to completion, with a decreased variability between student scores. Student satisfaction was high, with 100% of students who completed the primer agreeing it made them more prepared for the endocrine elective and all students recommending other electives create similar primers as well.
Conclusion: The endocrine primer standardized students’ endocrinology knowledge and enhanced satisfaction with the endocrinology elective. This self-paced learning opportunity was well received by medical students and should be included in other clinical electives. This pilot study will be expanded to a larger sample size and incorporate internal medicine residents on the endocrinology elective. We also plan to review faculty satisfaction before and after the primer was initiated.
Endocrinology in the Time of Coronavirus: A Virtual Endocrinology Elective for Medical Students
Authors: Moxley Meaghan C , Lamos Elizabeth , Malek Rana 
Published: May 2021

Abstract
Introduction: During the COVID-19 pandemic, the Association of American Medical Colleges recommended that medical students halt in-person learning. Our institution created a competency based virtual endocrinology elective to provide continued clinical experience with a focus on type 2 diabetes (T2DM) and health equity in diabetes care.
Methods: A 4-week virtual endocrinology elective alternated between different mini-rotations to maximize exposure to inpatient and outpatient endocrine care, as well as self-directed and faculty/fellow directed educational experiences. Post-elective surveys assessed student satisfaction with elective components and change in comfort levels with T2DM management and social determinants of health (SDH) on diabetes care.
Results: Overall, 87% (n=13) of students were “extremely satisfied” with the elective. Increased comfort was seen with management of type 2 DM and the impact of SDH on DM care (DM 88% neutral/uncomfortable to 94% comfortable, SDH 50% neutral/uncomfortable to 94% comfortable). Students were satisfied with the quality of patient care and requested opportunities for more direct involvement.
Conclusions: This virtual endocrine elective shows that curricula can be creatively designed to educate students in endocrinology, assess students across core competencies, and demonstrate impacts of telehealth and social determinants of health on endocrine and patient care.
Glycaemic Control in Children and Adolescents With Type 1 Diabetes Following a Single Telehealth Visit:What Have We Learned From the COVID-19 Lockdown?
Authors: Rachmiel Marianna , Lebenthal Yael , Mazor-Aronovitch Kineret , Brener Avivit , Levek Noah , Levran Neria , Chorna Efrat , Dekel Michal , Barash Galia , Landau Zohar , Pinhas-Hamiel Orit 
Published: May 2021

Abstract
Aims: Children with chronic diseases were unable to receive their usual care during COVID-19 lockdown. We assessed the feasibility and impact of telehealth visits on the time-in-range (TIR) of pediatric individuals with type 1 diabetes (T1D). Methods: An observational multicenter real-life study. Patients scheduled for an in-clinic visit during the lockdown were offered to participate in a telehealth visit. Sociodemographic, clinical, continuous glucose monitor and pump data were recorded 2 weeks prior and 2 weeks after telehealth visit. The primary endpoint was change in relative-TIR, i.e change in TIR divided by the percent of possible change (∆TIR/(100-TIRbefore)*100). Results: The study group comprised 195 individuals with T1D (47.7% males), mean±SD age 14.6±5.3 years, diabetes duration 6.0±4.6 years. Telehealth was accomplished with 121 patients and their parents (62.0%); 74 (38.0%) did not transfer complete data. Mean TIR was significantly higher for the two-week period after the telehealth visit than for the two-week period prior the visit (62.9±16.0, p&lt;0.001 vs. 59.0±17.2); the improvement in relative-TIR was 5.7±26.1%. Initial higher mean glucose level, lower TIR, less time spent at &lt;54 mg/dl range, longer time spent at 180–250 mg/dl range, higher daily insulin dose and single parent household were associated with improved relative-TIR. Multiple regression logistic analysis demonstrated only initial lower TIR and single-parent household were significant, odds ratio: -0.506, (95%CI -0.99,-0.023), p=0.04 and 13.82, (95%CI 0.621, 27.016), p=0.04, respectively.
Conclusions: Pediatric patients with T1D benefited from a telehealth visit during COVID-19. This modality and its benefit should be employed, and used in the future as well. However, this modality is not yet suitable for a considerable proportion of patients.
High Prevalence of Diabetes in Hospitalized Patients With COVID-19 and Its Association With Greater Severity of COVID-19 in Delhi, India
Authors: Mithal Ambrish , Jevalikar Ganesh , Sharma Rutuja , Singh Anshu , Farooqui Khalid J , Dewan Arun , Budhiraja Sandeep 
Published: May 2021

Abstract
Abstract: India is home to 77 million people with diabetes and has a large number of COVID 19 cases, albeit with a low fatality (&lt;1.5%). Little Indian data is available about the prevalence of diabetes in COVID 19 and its impact on outcomes. This observational prospective study (approved by the Institutional Ethics Committee) was carried out in a designated COVID facility, largely catering to middle and upper socioeconomic classes. A total of 401 (125 F, mean age 54 y, range 19–92 y) consecutive adults hospitalized with COVID-19 infection as proven by positive nasal swab for SARS-CoV2 by RT-PCR were included. Diabetes mellitus was diagnosed either by known history or HbA1c≥6.5%. Severity was assessed using the WHO ordinal scale1. Clinical outcomes and markers of inflammation were compared between diabetes and non-diabetes groups. Out of 401 patients, 210 (52.4%) had either diabetes (189,47.1%) or hyperglycemia requiring insulin treatment (21, 5.2%). 152 (37.9%) reported known diabetes, and 37 (9.2%) had preexisting but undiagnosed diabetes (HbA1c≥ 6.5%). People with diabetes were significantly older (mean age 59.9 vs 47.7 y), and had a higher proportion of men (74.6 vs 63.7 %), hypertension (58.7 vs 25%), CAD (13.8 vs 4.2%), and CKD (5.3 vs 0.9%) and a higher mean baseline severity score (3.4±0.7 vs. 3.2±0.5, p-0.000). The diabetes group had a higher number of severe cases (WHO scale≥5) (20.1% vs 9%, p-0.002) and higher mortality (6.3 vs 1.4%, p-0.015). A higher proportion of the diabetes group required ICU admissions (24.3 vs 12.3%, p-0.002), glucocorticoid therapy (78.3 vs 54.2%, p-0.000), oxygen administration (53.4 vs 28.3%, p-0.000), inotropic support (7.4 vs 2.4%, p-0.019), and renal replacement therapy (3.7% vs 0,p-0.005). The mean duration of hospital stay was higher for the diabetes group (10.4 vs 9.1 days, p-0.016). Of those who died, 12/15 (80%) had diabetes. Baseline Hba1c (n=331) showed a significant correlation with outcome severity scores (r 0.136, p-0.013). Markers of inflammatory response, CRP (41.0±4.4 vs. 19.4±3.8, p-0.000), ferritin (404.8±41.6 vs. 258.8±40.2, p-0.012), IL6 (65.5±11.6 vs. 26.9±4.4, p-0.002), LDH (321.8±10.1 vs. 286.8±8.4, p-0.008) were significantly higher in the diabetes group. Procalcitonin and D Dimer did not differ significantly. In conclusion, we report the highest prevalence of diabetes in a hospitalized COVID-19 population so far. The diabetes group had more severe disease and greater mortality. Baseline HbA1c correlated with poor outcomes. The comorbidities could have contributed to these poorer outcomes in the diabetes group. Strategies to improve outcomes in this pandemic it is imperative to include screening for and better control of diabetes.
Reference: 1 https://www.who.int/blueprint/priority-diseases/key-action/COVID-19_Treatment_Trial_Design_Master_Protocol_synopsis_Final_18022020.pdf
Impact of COVID 19 National Lockdown on Glycaemic Control in Children and Adolescents With Type 1 Diabetes (T1DM): A Retrospective Review at a Large UK Teaching Hospital
Authors: Lawrence Neil Richard , Natarajan Anuja , Petkar Razia , Joseph Lovlin 
Published: May 2021

Abstract
Introduction: The coronavirus disease global pandemic led to national lockdown in the United Kingdom on 23rd March 2020. We compared the glycaemic control of children and adolescents with Type 1 diabetes (T1DM) at Doncaster & Bassetlaw Teaching Hospitals in the 12 weeks prior to the lockdown, to the 12 weeks following lockdown. Methods: HbA1c result 3 months following lockdown was compared to the last HbA1C prior to lockdown. Data from Continuous Glucose Monitors (CGMs), Flash Glucose Systems (FGS) and those performing Self-Monitoring of Blood Glucose (SMBG) were compared alongside changes to patient contact that occurred. Results: In 264 patients under 20 years of age across both hospitals in the Trust, face-to-face consultations decreased (245 vs 151, 39%), and remote consultations increased (1751 vs 2269, 30%) (χ 2 p&lt;0.001). Excluding those within a year of diagnosis, 122 had paired HbA1c results, and 80 had more than 70% of glucose monitoring data available. HbA1c levels decreased (67.4 mmol/mol vs 61.3 mmol/mol, p&lt;0.001) and glucose monitoring data showed lower mean glucose after lockdown (9.7mmol/L vs 9.5mmol/L, p=0.034) with lower standard deviation (4.4mmol/L vs 4.2mmol/L, p&lt;0.001). Proportion of time in range (3.9mmol/L to 10mmol/L) increased (n=47, 55.2% vs 58.0%, p=0.017), with no change to time below range (4.8% vs 5.0%, p=0.495). Conclusion: Glycaemic control improved in the 12 weeks following national lockdown. This demonstrates the difficulties faced by patients and carers managing T1DM around school pressures, meals away from home, social life and peer pressure. Increased remote contact with patients with T1DM has not been detrimental to glycaemic control.
In-Hospital Glycemic Dysregulation Associated With Worse Outcomes in COVID-19
Authors: Rodriguez Lisette Patricia , Farhangi Vida , Braham Julaine , Smith Robert A , Wiese-Rometsch Wilhelmine 
Published: May 2021

Abstract
Introduction: Evidence establishes that COVID-19 patients with DM2 are at increased risk for severe disease and worse outcomes. Peer reviewed data is sparse comparing glycemic control and clinical outcomes among COVID-19 patients with vs. without DM2, and thus we sought to address this gap. Methods: We selected patients at least 18 years old who expired or were discharged between March 16, 2020 through September 15, 2020. Principal analysis compared glycemic patterns among patients with DM2 vs. non-DM2. Median, coefficient of variation (CV), maximum and minimum glucose parameters were computed to characterize longitudinal glycemic patterns. Logistic regression modeling identified significant (p&lt;.05) associations between composite outcome vs. glycemic parameters and putative risks for progression to severe COVID-19. Receiver operating characteristic (ROC) curve identified cut points for glycemic parameters. Cox regression models were employed to control for significant confounders. Continuous data summarized as median was compared using Kruskal-Wallis test. Discrete data were compared with Pearson’s chi-square test. Two-tailed p&lt;.05 was significant. Results: Among 494 patients, 157 (32%) had DM2 with no intergroup differences in age (68 [56–79]), sex (52% male, 48% female), or race (68% Caucasian, 19% Other, 13% African American). Insulin was administered to DM2 (93%) and non-DM2 (54%) patients (p&lt;.0001). Comorbidities were more prevalent in DM2, including cardiovascular (68% vs. 54%, p=.003), renal (72% vs. 52%, p&lt;.0001) and obesity (51% vs. 38%, p&lt;.0001). Markers including D-dimer (0.98 [0.61–1.95] mg/L), lactate dehydrogenase (308 [230–392] U/L), ferritin (436 [174–856] ng/mL), and triglycerides (172 [109–239] mg/dL), were not different in DM2 vs. non-DM2 (p&gt;.05). CRP was greater in patients with (8.6 [3.6–14.6]) vs. without (6.1 [2.0–12.6]) DM2 (p=.005). Baseline glucose in DM2 (163 [121–253] mg/dL) vs. non-DM2 (107 [96–124] mg/dL) was significantly greater, with former an independent predictor of composite outcome (p=.0005). Cox modeling of other glucose parameters in DM2 vs. non-DM2 demonstrated various impact regarding risk for composite outcome including median (155 [128–209], p=.46) vs. (103 [94–118], p=.09); coefficient of variation (28 [19–38], p=.08) vs. (15 [9–20], p=.002); maximum (252 [187–362], p=.0005) vs. (129 [110–156], p=.002); and minimum (99 [79–128], p=.95) vs. (89 [81–98], p=.02). The unified baseline glucose cut point for composite outcome risk controlled for significant covariates was 138 gm/dL (p&lt;.0001), which included respectively 20% and 10% of patients with and without DM2. Conclusion: Glycemic dysregulation in COVID-19 patients is independently associated with ICU admission and/or hospital mortality. Presence of DM2 amplifies glycemic dysregulation, but risk stratification appears warranted in all COVID-19 patients.