bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computational Design of Peptide Inhibitors Targeting the SARS-CoV-2 Main Protease
Authors: Das Chainee , Mattaparthi Venkata Satish Kumar 
Published: June 2024

Background:
The novel coronavirus disease also known as COVID-19 was first detected
in December 2019 in Wuhan, China and was caused by the severe acute respiratory syndrome coronavirus
2 (SARS-CoV-2) and its effect can still be seen in some parts of the world due to the lack of
effective antiviral drugs and vaccines for treatment and controlling the pandemic. Chymotrypsin-like
protease (3CLpro), also known as the main protease (Mpro) of SARS-CoV-2 plays a vital role during
its replication process of the pathogen’s lifecycle and is therefore considered a potential drug target
for COVID-19. Hence, targeting the Mpro is an appealing approach for drug development because of
its significant role in viral replication and transcription and therefore can act as an attractive drug
target to combat COVID-19 as confirmed by researchers through numerous studies so far. Although
small molecules dominate the field of drug market so far, peptide inhibitors still represent a class of
promising candidates because of their similarity to endogenous ligands, high affinity, and low toxicity.
It has been validated that therapeutic peptides can effectively and selectively inhibit the proteinprotein
interactions in viruses. Hence, it is necessary to design potential peptide inhibitors in order to
inhibit the impact of the disease.

Objective:
To design peptide inhibitors against the SARS-CoV-2 Main Protease using computational
methods

Methods:
This study involves the development of potential target peptides that can act against the
Mpro in a competitive mode against histone deacetylase (HDAC2) which had a high-confidence
interaction with Mpro. Based on the interaction between Mpro and HDAC2, 13 peptides were designed
out of which based on toxicity, binding affinity and binding site prediction, two peptides
(peptide2 and peptide4) were screened and subjected to MD simulation.

Results:
Our study shows that the two peptides bind to the active site of the Mpro and it attains a
higher stability upon binding to the peptides. We also found out that the Mpro has a strong binding
affinity with both the peptides (GBTOT = -72.85 kcal/mol for Mpro-peptide2 complex and GBTOT = -
46.36 kcal/mol for the Mpro-peptide4 complex).

Conclusion:
Even though declaring those peptides as future potent drug candidates would require
more analysis and trials, our analysis will surely add value to the future findings and these findings
could aid in the development of novel SARS-CoV-2 Mpro peptide inhibitors. These findings could
aid in the development of novel SARS-CoV-2 Mpro peptide inhibitors.
Exploring Older Adults' Perceptions of Using Digital Health Platforms for Self-Managing Musculoskeletal Health Conditions: Focus Group Study
Authors: Clohessy Sophie , Kempton Christian , Ryan Kate , Grinbergs Peter , Elliott Mark T 
Published: June 2024

Background
Digital technologies can assist and optimize health care processes. This is increasingly the case in the musculoskeletal health domain, where digital platforms can be used to support the self-management of musculoskeletal conditions, as well as access to services. However, given a large proportion of the population with musculoskeletal conditions are older adults (aged ≥60 years), it is important to consider the acceptability of such platforms within this demographic.

Objective
This study aims to explore participants’ opinions and perceptions on the use of digital platforms for supporting the self-management of musculoskeletal conditions within older adult (aged ≥60 years) populations and to gather their opinions on real examples.

Methods
A total of 2 focus groups (focus group 1: 6/15, 40%; focus group 2: 9/15, 60%) were conducted, in which participants answered questions about their thoughts on using digital health platforms to prevent or manage musculoskeletal conditions. Participants were further presented with 2 example scenarios, which were then discussed. Interviews were audio recorded, transcribed, and analyzed thematically. Participants were aged ≥60 years and with or without current musculoskeletal conditions. Prior experience of using smartphone apps or other digital health platforms for musculoskeletal conditions was not required. Focus groups took place virtually using the Teams (Microsoft Corp) platform.

Results
A total of 6 themes were identified across both focus groups: “experiences of digital health platforms,” “preference for human contact,” “barriers to accessing clinical services,” “individual differences and digital literacy,” “trust in technology,” and “features and benefits of digital health technologies.” Each theme is discussed in detail based on the interview responses. The findings revealed that most participants had some existing experience with digital health platforms for preventing or managing musculoskeletal conditions. Overall, there was a lack of trust in and low expectations of quality for digital platforms for musculoskeletal health within this age group. While there was some concern about the use of digital platforms in place of in-person health consultations, several benefits were also identified.

Conclusions
Results highlighted the need for better communication on the benefits of using digital platforms to support the self-management of musculoskeletal conditions, without the platforms replacing the role of the health care professionals. The concerns about which apps are of suitable quality and trustworthiness lead us to recommend raising public awareness around the role of organizations that verify and assess the quality of digital health platforms.
Measurement of Tremors for the Seismic Station of Gllogovc-Kosovo
Authors: HASI Nazmi , HASI Latif , CENA Besire 
Published: June 2024

To select a potential location for a future seismological station properly, it is of crucial importance to explore the existing local seismic tremor recorded by seismographs. This tremor/noise is referred to as seismic tremor, whereas it is necessary to define as precisely as possible its spectral characteristics. It is very important that the station location be as quiet as possible because the seismic noise can obscure the records at the selected location for seismic station. Therefore, in addition to other geophysical methods, it is of particular importance to define the spectral characteristics of the local tremor at the investigated sites.Seismic noise measurements were made at seismic station of Gllogovc - Kosovo. It is very important that the station location be as quiet as possible because the seismic noise can obscure the records at the selected 8 locations for seismic stations.Seismologists are necessary for such investigations.Considering the requirement regarding their sensitivity and resolution,geophones are not recommended to be used. Still, geophones were also used in these measurements for the purpose of comparing the obtained results. The most important requirement that should be fulfilled is that the instrumental noise of the seismometres be much lower than the level of the natural seismic noise at the location.
1006-P: Continuous Glucose Monitoring for High-Risk Type 2 Diabetes in the Hospital—The Cyber GEMS Randomized Controlled Trial Protocol
Authors: SPIERLING BAGSIC SAMANTHA R. , FORTMANN ADDIE L. , BASTIAN ALESSANDRA , BELASCO REBEKAH , SANDOVAL HALEY , LOHNES SUZANNE , TALAVERA LAURA , PHILIS-TSIMIKAS ATHENA 
Published: June 2024

Introduction & Objective: Continuous glucose monitoring (CGM) for inpatient management of type 2 diabetes (T2D) has been supported by small pilot studies but lacks confirmation by large randomized controlled trials. The Cloud-Based Real-Time Glucose Evaluation and Management System (Cyber GEMS) trial tests whether real-time CGM can improve time in, above, and below target glycemic range, and reduce hospital acquired infections.
Methods: This in-progress study is enrolling at 2 large disproportionate-share hospitals in Southern CA. Eligible patients are ≥18 years with T2D and on subcutaneous insulin with 3+ glucose ≥ 200 mg/dL. The CGM device is placed and validated against POCT using the %20/20 rule. The CGM transmitter sends data to a smartphone in a lock box at bedside that, in turn, transmits values to platforms for clinical management and evaluation purposes. Participants are randomized to usual care (UC) with point of care glucose testing (POCT) or Cyber GEMS with real-time CGM for glucose monitoring and management. In Cyber GEMS, CLARITY is used for clinical optimization by a remote diabetes RN specialist, the FOLLOW app on a unit iPad is used for real-time management by bedside RN, and a digital dashboard is used for real-time alert monitoring by a remote team. Blinded CGM is utilized in the UC group for outcome evaluation purposes only.
Results: N = 209 of 554 participants have completed the study. Participants are M = 61.3 ± 13.1 years of age, 59% male, 75% Hispanic; 58% reported an annual income &lt; $20,000. Participants had an average maximum glucose of M: 315 ± 80.6 mg/dL prior to enrollment, an T2D duration of M = 17.3 ± 12.1 years; 92% were CGM naive. Average duration in the study was 3.7 days.
Conclusion: The Cyber GEMS protocol is uniquely designed to evaluate the value and utility of real-time CGM for optimizing hospital glucose management in a high-risk, underserved T2D population. Lessons learned and implications for hospital based CGM use will be presented.

Disclosure
S.R. Spierling Bagsic: None. A.L. Fortmann: None. A. Bastian: None. R. Belasco: None. H. Sandoval: None. S. Lohnes: Consultant; Dexcom, Inc. L. Talavera: None. A. Philis-Tsimikas: Advisory Panel; Dexcom, Inc., Lilly Diabetes, Novo Nordisk, Sanofi, Medtronic, Bayer Inc.

Funding
NIH NIDDK (1R01 DK124427-01A1)
1023-P: Predictive Value of Admission Plasma Glucose and Hemoglobin A1c on Inpatient Glycemic Control Assessed by Continuous Glucose Monitoring (CGM) in Medicine and Surgery Persons with Diabetes
Authors: CASTRO-REVOREDO IRIS A. , ZHOU SIYU , URRUTIA MARIA A. , VELLANKI PRIYATHAMA , IDREES THAER , ZABALA ZOHYRA , GALINDO RODOLFO J. , PENG LIMIN , UMPIERREZ GUILLERMO 
Published: June 2024

Predictive Value of Admission Plasma Glucose and Hemoglobin A1c on Inpatient Glycemic Control Assessed by Continuous Glucose Monitoring (CGM) in Medicine and Surgery Persons with Diabetes
To determine the predictive value of admission blood glucose (BG) and A1C on inpatient glycemic control assessed by CGM in general medicine and surgery persons with T2D, we combined data from two randomized controlled trials of insulin-treated patients wearing a Dexcom G6 CGM. The primary outcome was optimal glycemic control defined as the percent time in range (TIR, 70-180 mg/dL) ≥70% without hypoglycemia (&lt;70 mg/dL). Logistic regression models were used to evaluate the predictive role of admission BG &lt; 180, 181-250, and &gt;251 mg/dL as well as A1C (&lt;7, 7-9, and &gt;9%).
Among 262 persons (medicine 73%, admission BG 222.4±121 mg/dL, A1C 9.4±2.4%), good glycemic control was achieved in 24%, 7.7%, and 7.5% of patients with admission BG &lt;180, 181-250 and &gt;251 mg/dL; and in 26%, 19%, and 8.6% in those with admission A1C &lt;7%, 7-9%, and &gt;9%, respectively. There were no differences in the rate of hypoglycemia, length of hospital stay (LOS), or hospital complications, Table.
Conclusion: Persons with higher admission BG and HbA1c levels had lower odds of achieving good glucose control (TIR 70-180 mg/dL ≥70% without hypoglycemia); however, there were no differences in hypoglycemia, LOS, or hospital complications compared to those with admission glucose &lt;180 mg/dl or HbA1c &lt;7%.
Table. Hospital glycemic control according to admission glucose and A1C values.
*Good Control: Mean daily glucose 70-180 mg/dL, without hypoglycemia &lt; 70 mg/dLTIR: Time in range; TAR: time above range; TBR: time below range; LOS: length of stay

Disclosure
I.A. Castro-Revoredo: None. S. Zhou: None. M.A. Urrutia: None. P. Vellanki: Consultant; Eli Lilly and Company. T. Idrees: None. Z. Zabala: None. R.J. Galindo: Consultant; Abbott. Other Relationship; Dexcom, Inc. Consultant; Bayer Inc. Other Relationship; Novo Nordisk, Eli Lilly and Company. Consultant; Boehringer-Ingelheim, AstraZeneca. L. Peng: None. G. Umpierrez: Research Support; Abbott, Bayer Inc., Dexcom, Inc., AstraZeneca. Advisory Panel; Dexcom, Inc.
1035-P: Cost-Effectiveness of Real-Time CGM vs. Self-Monitoring of Blood Glucose in People with Insulin-Treated Type 2 Diabetes from a U.S. Payor Perspective
Authors: ALSHANNAQ HAMZA , NORMAN GREGORY J. , LYNCH PETER M. 
Published: June 2024

Introduction: Diabetes and its complications cost the US healthcare system $412.9 billion in 2022. The use of RT-CGM systems in diabetes management is associated with improvements in glycemic outcomes for people with insulin-treated T2D. We aim to investigate the cost-effectiveness of RT-CGM systems from a US payor perspective.
Methods: Using the IQVIA Core Diabetes Model v10.0, we projected clinical outcomes and direct medical costs over a lifetime horizon from a US payor perspective. Cohort characteristics and clinical inputs were sourced from a large US retrospective cohort study. Clinical parameters include an A1C effect of -0.56% favoring RT-CGM, severe hypoglycemic events rates of 0.04 and 0 Per Person-Year (PPY) for SMBG and RT-CGM, respectively, and DKA rates of 0.025 and 0 PPY, respectively. The costs of glucose monitoring are based on Medicare pricing and 80% reimbursement (HCPCS codes A4239 and A4253). A utility for the avoidance of finger sticks (0.03) and fear of hypoglycemia reduction (0.025) were applied to users of RT-CGM.
Results: The model projects RT-CGM users to have higher quality-adjusted life years by 0.769 with incremental costs of $16,019, and an incremental cost-effectiveness ratio (ICER) of 20,825, which is below the willingness to pay threshold (WTP) of $50,000. The relative reduction in the total number of events due to RT-CGM use for diabetes eye, renal, neuropathy, and cardiovascular complications was 17.0%, 20.0%, 8.7%, and 2.4% respectively. RT-CGM remained cost-effective under the $50,000 WTP even when its cost was increased by 85% (+$2,097). Sensitivity analysis for reducing RT-CGM costs by 10%, 20%, and 30% resulted in ICERs of 17,425, 14,020, and 10,616 respectively.
Conclusions: RT-CGM systems are cost-effective and project cost-savings due to a reduction in acute diabetes events, and microvascular and macrovascular complications. Our findings support access to RT-CGM in US payor policies.

Disclosure
H. Alshannaq: Employee; Dexcom, Inc. Stock/Shareholder; Unicycive Therapeutics. G.J. Norman: Employee; Dexcom, Inc. P.M. Lynch: Employee; Dexcom, Inc. Stock/Shareholder; Dexcom, Inc.
1040-P: The Value of the Guideline-Recommended Management of Type 2 Diabetes—A Novel Population-Level System Dynamics Approach
Authors: MCEWAN PHILIP , PADGETT THOMAS , GOULDEN SCOTT R. , CHUBB BARRIE , MANSINHO JOANA N. , REN HONGYE 
Published: June 2024

Introduction and Objectives: Current clinical guidelines advocate a holistic approach (HA) to type 2 diabetes (T2D) management based on glucose control, cardiovascular (CV) risk, chronic kidney disease (CKD) progression and body weight. Conventional approaches to quantifying value are likely to underestimate the benefit of treating diabetes in line with guideline recommendations due to the narrow focus of traditional health economic evaluations. With the prevalence of T2D projected to rise, we quantified the value of adopting a HA strategy across the health care system compared with a traditional glucose management (GM) strategy, from a multi-stakeholder perspective.
Methods: We developed a population-level T2D system dynamics model calibrated to UK incidence and prevalence data. T2D outcomes were predicted to 2040, using rates from UKPDS. The cardiorenal benefits of HA were incorporated using odds ratios from meta-analysis of contemporary CV outcomes trials. The impact of population growth, an ageing population, and the adoption of a HA versus GM strategy on healthcare resource use, patient outcomes, societal productivity, environment, and total costs were assessed.
Results: Modelled UK prevalence of diagnosed T2D in adults is expected to increase from 3.4M to 4.0M between 2023 and 2040; a GM strategy estimates an 18.6% and 17.5% increase in CV and microvascular (MV) complications, respectively, with 46.16 CV events and 4.88 MV events annually per 1,000 patients, by 2040. Applying a HA strategy to eligible patients reduced this to 42.11 CV events and 4.86 MV events annually per 1,000 patients, resulting in a reduction in direct healthcare costs of £1.68B, 171,225 fewer hospitalizations and 1.32M bed days saved, a reduction in lost income of £266.20M and a gain of 2.18M workdays.
Conclusion: The cardiorenal protection offered by new T2D therapies has the potential to confer benefits to multiple stakeholders across the healthcare system.

Disclosure
P. McEwan: Consultant; AstraZeneca, Novo Nordisk A/S, Boehringer-Ingelheim, GlaxoSmithKline plc, Bristol-Myers Squibb Company, Rocket Pharmaceuticals Inc. T. Padgett: Stock/Shareholder; GlaxoSmithKline plc, Novo Nordisk A/S. S.R. Goulden: Employee; Novo Nordisk A/S. Stock/Shareholder; Novo Nordisk A/S. B. Chubb: Employee; Novo Nordisk A/S. J.N. Mansinho: Employee; Novo Nordisk A/S. H. Ren: Employee; Novo Nordisk.
1041-P: Assessing the Value of Managing Diabetic Kidney Disease from a U.S. Health Care Perspective
Authors: MCEWAN PHILIP , PADGETT THOMAS , EVANS MARC 
Published: June 2024

Introduction: The management of diabetic kidney disease (DKD) is associated with considerable resource utilization. The objective of this study was to estimate the economic value associated with modifying the progression of DKD by attenuating the rate of decline of eGFR.
Methods: We developed a deterministic model utilizing published estimates of type 2 diabetes and chronic kidney disease (CKD) stratified by stages: stage 1/2, stage 3a, stage 3b and stage 4/5. Patient characteristics and mean annual decline in eGFR were aligned to the placebo arm of DECLARE-TIMI 58 (-2.44 ml/min/1.732). Diabetes-specific and all-cause mortality were captured using UKPDS risk equations. CKD stage-specific costs and changes in health utility were drawn from US published sources. Costs (indexed to 2023) and quality adjusted life years (QALYs) were both discounted at 3%.
Results: The table illustrates the absolute lifetime costs/QALYs associated with the natural history of DKD, and the change in costs/QALYs from attenuating the rate of eGFR decline.
Discussion: Attenuating the decline of eGFR in DKD at the population level has the greatest health gain and cost saving in early disease stages. On an individual basis, optimal cost saving and health gains occur at stage 3; in stage 4/5 attenuating eGFR decline results in health gain, but also additional costs due to the cost of managing advanced DKD.

Disclosure
P. McEwan: Consultant; AstraZeneca, Novo Nordisk A/S, Boehringer-Ingelheim, GlaxoSmithKline plc, Bristol-Myers Squibb Company, Rocket Pharmaceuticals Inc. T. Padgett: Stock/Shareholder; GlaxoSmithKline plc, Novo Nordisk A/S. M. Evans: Consultant; Novo Nordisk A/S, AstraZeneca, Eli Lilly and Company, Boehringer-Ingelheim, Sanofi.
1045-P: Cost-Effectiveness of Adjuvanted RSVPreF3 Vaccination in Adults Aged 50–59 Years with Diabetes in the United States
Authors: SINGER DAVID , LA ELIZABETH , GRAHAM JONATHAN , GRACE MEI , POSTON SARA , MOLNAR DANIEL 
Published: June 2024

Introduction & Objective: Older adults and adults with comorbidities, such as metabolic diseases, are at increased risk of severe respiratory syncytial virus (RSV) disease. This study assessed the cost-effectiveness of adjuvanted RSVPreF3 vaccination in adults 50-59 years of age (YOA) with diabetes in the US.
Methods: A Markov model was used to estimate costs and health outcomes over a 3-year time horizon from a societal perspective, comparing scenarios with and without one-time adjuvanted RSVPreF3 vaccination. Indirect costs and quality-adjusted life year (QALY) losses due to RSV-related death were modeled over the remaining lifetime. The population included 5,617,227 US adults 50-59 YOA with diabetes. Vaccination coverage of 50.1% was assumed, based on influenza vaccination coverage. Scientific literature and public sources were used to inform model inputs. Incremental cost and health outcomes were reported along with the incremental cost-effectiveness ratio (ICER), comparing adjuvanted RSVPreF3 vaccination to no vaccination.
Results: Over the 3-year time horizon, adjuvanted RSVPreF3 vaccination avoided an estimated 180,546 symptomatic RSV acute respiratory illnesses, including 144,676 lower respiratory tract disease cases, 108,392 RSV-related outpatient visits, and 7,841 RSV-related hospitalizations. Vaccination resulted in incremental total societal costs of -$39 million (M), including incremental direct and indirect costs of $623M and -$662M, respectively. Adjuvanted RSVPreF3 vaccination avoided 10,290 QALY losses and 551 RSV-related deaths. With improved health outcomes and lower societal costs, adjuvanted RSVPreF3 vaccination was dominant versus no vaccination (ICER &lt;$0 per QALY gained).
Conclusion: One-time adjuvanted RSVPreF3 vaccination resulted in improved health outcomes and reduced societal costs compared to no vaccination, suggesting it is cost-effective for the prevention of RSV in adults 50-59 YOA with diabetes.

Disclosure
D. Singer: Employee; GlaxoSmithKline plc. Stock/Shareholder; GlaxoSmithKline plc. E. La: Employee; GlaxoSmithKline plc. Stock/Shareholder; GlaxoSmithKline plc. J. Graham: Research Support; GlaxoSmithKline plc. M. Grace: None. S. Poston: Employee; GlaxoSmithKline plc. D. Molnar: Employee; GlaxoSmithKline plc.

Funding
GlaxoSmithKline Biologicals SA (VEO-000556)
1057-P: Improving Outcomes for People with Diabetes through Value-Based Endocrinology
Authors: TERRY DAVID 
Published: June 2024

Healthcare services for people with diabetes (PWD) in the US are fragmented and uncoordinated, leading to broad variability in outcomes and annual healthcare costs per PWD, on a risk adjusted basis. The objective of our work is to test the hypothesis that PWD do better and utilize less resources, i.e. fewer complications, ER visits and hospitalizations, when cared for by an Endocrinologist, than when they are cared for by other types of clinicians.
To test our hypothesis we analyzed 100% of the Medicare Part A & B claims data from January 2021 through June of 2023. Using this data we identified 12 million Medicare PWDs, and we attributed each of them to an Endocrinologist, a PCP, an Other physician type, or No physician. We then risk adjusted the population based on the CMS Risk Adjustment Factor (RAF) methodology, and assessed risk-adjusted complication rates and resource utilization by physician, and physician attribution type (Endocrinologist, PCP, Other, None).
Through our analysis we found that PWD who regularly see an Endocrinologist throughout the year have fewer complications and utilize significantly less expensive healthcare resources than PWD who don’t regularly see an Endocrinologist. Preliminarily, PWD regularly cared for by an Endocrinologist spend $3,120 per year less than those not regularly cared for by an Endocrinologist, on a risk adjusted basis.
Based on these findings it is important to increase Endocrinology clinical capacity and access by creating multi-disciplinary clinical teams led by Endocrinologists that include Diabetes Educators, Dietitians, Nurse Practitioners and Nurses with expertise in diabetes who can care for many more PWDs. It is also important to incentivize the development of this model by moving Endocrinology care away from FFS into Value-Based Care arrangements that reward Endocrinologists for improving care and reducing costs rather than for generating more visits.

Disclosure
D. Terry: Employee; Valendo Health.