bluuebunny/crossref_metadata_2025_split huggingface dataset:
Navigating Insulin Options for Diabetes Management
Authors: Rafi Ebne , Tranchito Lily , Hatipoglu Betul 
Published: February 2025

Abstract

Context
Insulin therapy is first-line therapy for people with type 1 diabetes and often used for people with type 2 diabetes. Over the years, there has been a surge in insulin products available for use. As a result, clinicians need to have a strong understanding of the differences between insulin agents to provide proper patient care.

Evidence Acquisition
We included population-level data and searched PubMed and Google Scholar databases for recent systematic reviews, meta-analyses, and original research articles.

Evidence Synthesis
Patients who present with severe hyperglycemia or signs consistent with a catabolic state such as weight loss or ketonuria should be initiated on insulin. Furthermore, patients with a hemoglobin A1c (HbA1c) level &gt;10% or an unclear diagnosis of type 1 diabetes should typically be treated with insulin. Insulin products differ mainly in their pharmacokinetic profiles and not mechanism of action. The literature suggests that differences in pharmacokinetics allow certain insulin products to be well equipped to address different clinical situations such as steroid-induced hyperglycemia, managing patients with severe chronic kidney disease or dialysis, and insulin pump therapy.

Conclusion
Understanding kinetic profiles of different insulin agents will allow clinicians to properly navigate options for either fasting or mealtime coverage. Furthermore, this foundational knowledge will be critical when applying insulin therapy in clinical scenarios such as steroid-induced hyperglycemia, kidney disease, and insulin pump management. Ultimately, this will allow clinicians and patients to create proper diabetes care plans and self-management skills.
SGLT2i and Cardiovascular Events in Patients With Concomitant Atrial Fibrillation and Diabetes: A TriNetX Cohort Study
Authors: Hsiao Yu-Yu , Chen Yun-Yu , Kuo Ming-Jen , Chien Yu-Shan , Li Guan-Yi , Wu Shang-Ju , Lin Wei-Lun , Chiu Shu-Fen , Li Cheng-Hung , Lin Jiunn-Cherng , Lin Ching-Heng , Huang Jin-Long , Hsieh Yu-Cheng , Chen Shih-Ann 
Published: February 2025

Abstract

Aims
Sodium-glucose co-transporter 2 inhibitors (SGLT2i) enhance cardiovascular outcomes in individuals with type 2 diabetes mellitus (T2DM). Whether such effects also occur in T2DM patients with atrial fibrillation (AF) remains unknown. We aimed to investigate SGLT2i use on cardiovascular outcomes in patients with concomitant AF and T2DM.

Methods
Patients with both AF and T2DM were identified from TriNetX, an international electronic medical record. Participants were divided into 2 groups according to their use of SGLT2i, at a 1:1 distribution through propensity score matching (PSM). The hazard ratio (HR) for clinical outcomes was determined using multivariate Cox hazards regression model.

Results
We studied 339 792 patients with AF and T2DM, with 32 945 (9.70%) SGLT2i users. Following PSM, 17 011 patients aged 68.4 ± 7.9 years were included in each group. After a 3-year follow-up, patients treated with SGLT2i showed significantly reduced risks of stroke (adjusted HR: 0.830, P &lt; .001), dementia (adjusted HR: 0.662, P &lt; .001), long-standing persistent AF (adjusted HR: 0.917, P &lt; .001), heart failure (adjusted HR: 0.833, P &lt; .001), and all-cause mortality (adjusted HR: 0.532, P &lt; .001).

Conclusion
The use of SGLT2i was associated with reduced risks of stroke, dementia, long-standing persistent AF, heart failure, and mortality in patients with both AF and T2DM. SGLT2i may be considered as a potential first-line therapy for this population.
A tiered approach to exome sequencing analysis in early-onset Primary Ovarian Insufficiency
Authors: McGlacken-Byrne Sinéad M , Suntharalingham Jenifer P , Ishida Miho , Buonocore Federica , del Valle Ignacio , Cameron-Pimblett Antoinette , Dattani Mehul T , Achermann John C , Conway Gerard S 
Published: February 2025

Abstract

Context
Establishing the genetic basis of early-onset primary ovarian insufficiency (EO-POI, &lt;25 years) is important, but defining variant pathogenicity is challenging.

Objective
To elucidate the genetic architecture of EO-POI in a unique, large cohort.

Setting
Young women with EO-POI (n=149; n=31 familial, n=118 sporadic) attending a specialist reproductive unit.

Design
Exome sequencing was performed. After filtering, variants were retained which were 1) rare/novel (minor allele frequency &lt;0.01%); 2) predicted pathogenic/likely pathogenic; and 3) enriched in the cohort. Each variant was assigned to a category: Category 1, variants in Genomics England Primary Ovarian Insufficiency PanelApp genes (n=69); Category 2, variants in other POI-associated genes (n=355) or Category 1 variants following unexpected inheritance patterns; and Category 3, homozygous variants in novel candidate POI genes.

Results
A total of 127 Category 1 or 2 variants were identified in 74 different genes (heterozygous 30.9%; homozygous 9.4%; polygenic 21.8%). In familial EO-POI, 64.7% (11/17 kindred) had a Category 1 or 2 variant identified (homozygous: STAG3, MCM9, PSCM3IP, YTHDC2, ZSWIM7; heterozygous: POLR2C, NLRP11, IGSF10, PRKD1, PLEC; polygenic: PDE3A, POLR2H, MSH6, CLPP). In sporadic EO-POI, 63.6% (n=75/118) women had a variant identified (21.2% (n=25) Category 1; 42.4% (n=50) Category 2). Novel POI candidate genes (Category 3) included PCIF1, DND1, MEF2A, MMS22L, RXFP3, C4orf33, and ARRB1.

Conclusions
The genetic basis of EO-POI is complex and affected genes span ovarian developmental processes from fetal life to adulthood. Establishing the pathogenicity of individual heterozygous variants can be challenging. However, some women have clear monogenic causes, particularly in familial POI with autosomal recessive inheritance. Others have potential polygenic causes. We describe novel candidate POI genes warranting further exploration.
Single-cell landscape of peripheral blood mononuclear cells in patients with Graves’ disease
Authors: Wang Yixuan , Zhang Xinjie , Ge Junfeng , Jin Jiajia , Zheng Zhijian , Li Jiaxuan , Wang Xiaowei , Zhang Shucui , Wang Zhe , Dong Guangguo 
Published: February 2025

Abstract

Background
Graves’ Disease (GD) is a thyroid-specific autoimmune disease and the most common cause of hyperthyroidism. Its pathogenesis is associated with the disruption of immune tolerance and autoantibody production. However, the mechanisms underlying immune abnormalities remain incompletely elucidated.

Methods
We employed single-cell RNA sequencing (scRNA-seq) and analyzed 22680 peripheral blood mononuclear cells (PBMCs) from eight GD patients and twelve healthy controls.

Results
Our results unveiled the single-cell landscape of PBMCs in GD patients, revealing substantial heterogeneity and changes in the cellular composition and function of PBMCs. We observed an increase in the proportion of CD16+ NK cells and memory cells in T and B lymphocyte subsets. This increase was accompanied by significantly enhanced functions, including cell activation, immune/defense responses, and inflammatory reactions. Additionally, we detected changes in the activity of transcription factors in various cell types, which were linked to the regulation of genes critical for immune and inflammation responses. Furthermore, we found a reduction in communication between NK cells and other immune cells, including CD4+ T cells, monocytes, and B cells, mediated by KIR-like inhibitory receptors, suggesting their involvement in the pathogenesis of GD.

Conclusions
Our study revealed characteristic alterations in the composition and function of immune cell subsets in the PBMCs of GD patients. These findings shed light on the mechanisms underlying immune dysregulation in GD.
The Power of Education to Reduce the Carbon Footprint of Volatile Anesthetics in Clinical Practice
Authors: Schwiethal Arne , Treskatsch Sascha , Michael Jannis , Höft Moritz , Spies Claudia D. , Koch Susanne 
Published: February 2025

BACKGROUND:
Due to their chemical nature as fluorinated hydrocarbon compounds, volatile anesthetics are highly potent greenhouse gases, with desflurane having by far the largest CO2-equivalent (CO2e) footprint. In everyday clinical practice, the CO2e footprint can easily be reduced through the increased use of propofol or sevoflurane as well as low- and minimal-flow techniques or through the more frequent use of regional anesthesia techniques. We wanted to assess to what extent educational measures on sustainability aspects of the use of volatile anesthetics had an impact on daily practice in anesthesiology departments and to what extent this influenced the hospital’s CO2e emissions.

METHODS:
We conducted an observational data analysis of the consumption of anesthetics (sevoflurane, desflurane, isoflurane, and propofol) at all 3 clinical Charité campuses in the period from 2015 to 2023. The CO2e emissions were calculated for sevoflurane, desflurane, and isoflurane. External and internal (top-down or bottom-up) educational measures focusing on sustainability in anesthesia took place from September 2018 on. Shifts in CO2e emissions related to the educational measures are shown in a run chart. The number of surgeries, surgery duration, and purchasing costs were included in the analysis.

RESULTS:
CO2e emissions of volatile anesthetics were reduced by 90.3% from the baseline epoch (years 2015–2017) before educational interventions took place to 2023: CO2e 1470 tons (mean 2015–2017), to 191 tons (2022) to 142 tons (2023). This change was brought about by the phasing out of desflurane and the use of propofol or sevoflurane and regional anesthesia where appropriate. The fastest and most sustainable changes were seen after internal top-down measures. The total cost of anesthetics also fell over the period under review (from €541,102/$594,238 in 2015 to €281,646/$309,303 in 2023).

CONCLUSIONS:
Educational measures for anesthesiologists about the climate-damaging effects of volatile anesthetics—especially desflurane—can significantly reduce CO2e emissions in anesthesia clinics. On the positive side, these measures have also reduced the annual costs for anesthetics.
Advanced Footwear Technology, but not Acute Ingestion of a Ketone Monoester, Improves Running Economy in Middle- and Long-Distance Runners
Authors: Brady Aidan J. , Moynagh Megan B. , Devenney Simon , Egan Brendan 
Published: February 2025

ABSTRACT

Purpose
This study examined the separate and combined effects of advanced footwear technology (AFT) and acute ingestion of a ketone monoester on running economy (RE), time-to-exhaustion (TTE), and other metabolic and cardiorespiratory parameters.

Methods
In a four-condition, placebo-controlled, randomized crossover design, 18 middle- and long-distance runners (male/female, 10/8, V̇O2peak: 59.4 ± 7.2 mL·kg-1·min-1) completed five 8 min stages of submaximal running (male: 10–14 km·h-1; female: 9–13 km·h-1) on a motorized treadmill, immediately followed by a ramp test to volitional exhaustion. Participants consumed 500 mL of either a 10% carbohydrate solution (CHO) or 500 mg·kg-1 body mass of an (R)-3-hydroxybutyl (R)-3-hydroxybutyrate ketone monoester with flavored water (KME) 20 min before exercise, and an additional 300 mL of the 10% carbohydrate solution or 250 mg·kg-1 body mass of KME during exercise, while wearing either Nike Pegasus Turbo (PEG) or Nike ZoomX Vaporfly Next% 3 (VAP) running shoes. The four randomized conditions were PEG+CHO, PEG+KME, VAP + CHO, and VAP + KME.

Results
RE was significantly improved during the third and fourth submaximal running stages in VAP + CHO and VAP + KME compared to PEG+CHO and PEG+KME (all P < 0.05; ES = 0.53-0.84). RE was also improved during the fifth submaximal running stage in VAP + KME compared to PEG+CHO, and in VAP + CHO and VAP + KME compared to PEG+KME (all P < 0.05; ES = 0.56-0.66). No differences in RE were found between CHO and KME conditions. TTE was significantly longer in VAP + CHO (381 ± 125 s) than PEG+CHO (356 ± 140 s; ES = 0.18, P = 0.023) and PEG+KME (329 ± 131 s, ES = 0.40, P < 0.001) and in VAP + KME (375 ± 125 s) than PEG+KME (ES = 0.35, P < 0.001).

Conclusions
AFT, but not the acute ingestion of a ketone monoester, improved the RE of trained male and female middle- and long-distance runners at submaximal running speeds.
Solving Heat Stress in Sport: Intermittent Cold Air Exposure Mitigates Deterioration of the Autonomic Nervous System in American Football Athletes
Authors: Renaghan Eric , Wishon Michael J. , Wittels Harrison L. , Hecocks Dustin , Galasso Peter J. , Ren Tom , McDonald Samantha M. , Feigenbaum Luis A. , Wittels S H. 
Published: February 2025

ABSTRACT

Objectives
Cooling interventions mitigating heat-related declines in autonomic nervous system (ANS) function are understudied in American football.

Methods
This study exposed fifty, collegiate male athletes during their 2023 season to two bouts of cold air via air-conditioning prior to (60 mins) and during (5 min) training sessions in a hot and humid climate. Armband monitors, (Warfighter MonitorTM, Tiger Tech Solutions, Inc., Miami, FL, USA), were used to continuously measure core temperature (°C) during training and baseline heart rate (HR), HR recovery and HR variability (HRV) 24 hours post training. Two HRV time-domain indices were estimated: root mean square of the standard deviation of the NN interval (rMSSD) and the standard deviation of the NN interval (SDNN). These data (2023) were then compared to data collected throughout the previous season (2022) during which players were not provided a cold-air intervention. As such, the 2022 cohort served as a “control” group.

Results
Linear regression models no statistically significant associations at the following core temperature thresholds: ≥ 37.0 °C (baseline HR: p = 0.74; HR recovery: p = 0.71, rMSSD: p = 0.74; SDNN: p = 0.78), ≥ 38.0 °C baseline HR: p = 0.74; HR Recovery: p = 0.74; rMSSD: p = 0.68 and SDNN: p = 0.89) and ≥ 39.0 °C: baseline HR: p = 0.75; HR Recovery: p = 0.82; rMSSD: p = 0.78 and SDNN: p = 0.83). Compared to the 2022 season, the athletes spent considerably less time training under the higher core temperature thresholds (≥ 38 °C: 19.5 min vs 9.7 min; ≥ 39 °C: 10.5 min vs 0.9 min), respectively, despite longer overall training duration, (161.1 min vs 187.4 min).

Conclusions
Our findings suggest that incorporating bouts of cold air exposure when training in high heat and humidity may mitigate the established heat-related deterioration in ANS function.
An Economic Model of a Decentralized Exchange with Concentrated Liquidity
Authors: Hasbrouck Joel , Rivera Thomas J. , Saleh Fahad 
Published: February 2025

We develop an economic model of a decentralized exchange with concentrated liquidity (e.g., Uniswap v3 and v4), with a particular focus on the economics of liquidity provision. We demonstrate that providing liquidity for a risky/risk-free asset pool is comparable to investing in a covered call, except that the call option therein is sold at intrinsic rather than market value. Hence, when providing liquidity, liquidity providers forgo the time premium of the call option in exchange for fees, and thus equilibrium liquidity provision decreases in the time premium. Finally, we provide an expression for equilibrium liquidity provision that is useful for empirical work. This paper has been This paper was accepted by Lin William Cong for the Special Issue on Digital Finance.
Change-Point Detection in Dynamic Networks with Missing Links
Authors: Enikeeva Farida , Klopp Olga 
Published: February 2025

Unveiling Hidden Shifts: Detecting Change Points in Dynamic Networks with Missing Links Dynamic networks are ubiquitous in a world increasingly driven by interconnected systems from social media platforms to financial transactions, transportation systems, and cybersecurity infrastructures. Unlike static entities, these networks evolve, often undergoing abrupt structural changes. Detecting these changes is essential as they can signal critical events, such as cyberattacks or shifts in user behavior. The challenge becomes even greater when dealing with incomplete data, a common reality in large-scale networks. Missing links, from nonresponses or privacy concerns, create uncertainty, complicating the identification of structural changes. The paper “Change-Point Detection in Dynamic Networks with Missing Links” tackles this issue with a robust framework based on the matrix CUSUM test statistic. This novel methodology is adaptable to expanding networks and resilient to missing data. It detects structural shifts with minimax optimality, ensuring theoretical robustness. Extensive simulations and real-world examples reveal that the proposed approach outperforms existing methods. It provides a valuable tool for monitoring dynamic networks, detecting fraud, and spotting emerging trends.
Development of ethanol analysis in cough syrup medicine by colorimetric method
Authors: Sultan Siti Fatimah , Susanti Hari , Mohamed Farahidah , Salamah Nina 
Published: February 2025

Cough syrup is a pharmaceutical preparation often containing ethanol as a solvent. However, the presence of ethanol in the drug can cause safety issues. This study aims to develop and validate a colorimetric method for determining ethanol in cough syrup. Cough syrup samples from different brands were analyzed using the method. The Visible spectrophotometric method uses the oxidation reaction of ethanol with potassium dichromate in an acidic condition. Method validation was conducted, including linearity, precision, accuracy, limit of detection (LOD), and limit of quantification (LOQ). The results showed this method had good linearity (r > 0.99) with a concentration range of 0.48 – 5.76 % (b/v). UV-Vis spectrophotometric method showed good precision and accuracy with SD = 0.0014, RSD = 0.4046 %, and % recovery = 99.99 %, while LOD = 0.1074 % and LOQ = 0.3253 %. This study concludes that the colorimetric method can be used as a valid and complementary method for analyzing ethanol content in cough syrup, providing important information for producers and consumers regarding product safety.

Keywords: Analytical method validation, Cough syrup, Ethanol, Spectrophotometry.
How Do I Get to the Student Union? Developing Independent Navigation Skills in Students With an Intellectual or Developmental Disability
Authors: Mitchell Wendy R. , Deardorff Malarie , Sinclair Tracy , Wicker Melissa , McMillan Jeff 
Published: February 2025

Abstract
Navigating campus and the surrounding community may pose barriers to matriculation, engagement, and quality of life for students with disabilities. This intervention uses the student's smartphone device and a university map application to guide students as they navigate to specific destinations around campus (e.g., library, classroom buildings, restaurants, student union, and recreation centers). A single-case experimental withdrawal design (ABAB) was used to collect data for two participants. There was an immediate level change upon introduction of the intervention for both participants, indicating a functional relation. Results are suggestive that the presentation and application of wayfinding skills through technology can be successful and have the potential to support more independent lifestyles for persons with an intellectual or developmental disability.
Tiered Teacher Coaching to Promote Self-Determination in the Classroom
Authors: Kiblen Jessie C. , Shogren Karrie A. , Kurth Jennifer A. , Raley Sheida K. 
Published: February 2025

Abstract
Promoting self-determination has been shown to enhance outcomes for students with and without disabilities. The Self-Determined Learning Model of Instruction (SDLMI) is an evidence-based instructional model designed to promote self-determination in diverse contexts, including inclusive general education classrooms. SDLMI delivery requires training and ongoing support to enhance fidelity, teacher implementation skills, and positive student outcomes. Coaching supports the implementation and fidelity of an evidence-based instructional model, like the SDLMI. However, coaching supports must be tailored to implementers' needs. This article describes a three-tiered coaching model for the SDLMI that can inform teacher supports for effective SDLMI implementation. This three-tiered model expands the research-based SDLMI Coaching Model, providing a framework to individualize SDLMI supports to enhance teacher implementation and student outcomes.
Moderating and mediating mechanisms of the association between endogenous testosterone and aggression in youth: A study protocol
Authors: Calvete Esther , Cortazar Nerea , Orue Izaskun 
Published: February 2025

Background
The role of testosterone, particularly in combination with cortisol, in aggression remains debated. According to the general aggression model, hormones interact with other variables, such individuals’ knowledge structures, to predict aggression. This model may help explain inconsistent findings of previous research. Furthermore, the model posits that the influence of hormones on aggressive behavior is mediated by the individual’s internal state. Accordingly, the objectives of this study are to assess whether (1) testosterone and cortisol, alone and in interaction with aggression-related knowledge structures, predict aggression in a standardized laboratory paradigm and whether (2) this association is mediated by hostile attribution, anger, and arousal. By identifying key moderators and mediators, this study seeks to make a very novel contribution to the understanding of the role of testosterone in aggressive behavior. These objectives will also be assessed separately for males and females.

Methods
The Point Subtraction Aggression Paradigm will be used to assess aggression. The sample will include 110 youths aged 17–19 (50% male). Participants will provide saliva samples before and after completing the paradigm, along with measures of three aggression-related knowledge structures (justification of violence, hostility, and narcissism) collected before the paradigm. Measures of two mediators (hostile attribution, anger) will be obtained after completing the paradigm. Arousal levels (heart rate and skin conductance) will be recorded before, after, and while completing the paradigm. The hypotheses will be tested using path analysis models, examining both the testosterone/cortisol ratio and the interaction between testosterone and cortisol as well as both baseline hormone levels and changes in hormone levels.

Discussion
Although it may be limited by the use of saliva for measuring hormones, this study will enhance the current understanding of the role of testosterone and cortisol in aggressive behavior among youths by investigating novel hypotheses related to psychological moderating and mediating factors.