bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic phenotype of Stage 1 and Stage 2 type 1 diabetes using modelling of beta cell function
Authors: Galderisi Alfonso , Bonet Jacopo , Ismail Heba M , Moran Antoinette , Fiorina Paolo , Bosi Emanuele , Petrelli Alessandra 
Published: February 2025

Abstract

Context
Staging preclinical type 1 diabetes (T1D) and monitoring the response to disease-modifying treatments rely on the oral glucose tolerance test (OGTT). However, it is unknown whether OGTT-derived measures of beta-cell function can detect subtle changes in metabolic phenotype, thus limiting their usability as endpoints in prevention trials.

Methods
We characterized the metabolic phenotype of individuals with islet autoimmunity in the absence (Stage 1) or presence (Stage 2) of dysglycemia. Participants were screened at a TrialNet site and underwent a 5-point, 2-hour OGTT. Standard measures of insulin secretion (AUC C-peptide, HOMA2-B) and sensitivity (HOMA-IR, HOMA2-S, Matsuda Index) and oral minimal model derived insulin secretion (phi total), sensitivity (SI), and clearance were adopted to characterize the cohort.

Results
Thirty participants with Stage 1 and 27 with Stage 2 T1D were selected. Standard metrics of insulin secretion and sensitivity did not differ between Stage 1 and Stage 2 T1D, while the oral minimal model revealed lower insulin secretion (p&lt;0.001) and sensitivity (p=0.034) in those with Stage 2 T1D, as well as increased insulin clearance (p=0.006). A higher baseline phi total was associated with reduced odds of disease progression, independent of Stage [OR 0.92 (0.86, 0.98), p=0.016].

Conclusion
The oral minimal model describes the differential metabolic phenotype of Stage 1 and Stage 2 T1D and identifies phi total as a progression predictor. This supports its use as a sensitive tool and endpoint for T1D prevention trials.
Machine Learning–Based Survival Prediction Tool for Adrenocortical Carcinoma
Authors: Saygili Emre Sedar , Elhassan Yasir S , Prete Alessandro , Lippert Juliane , Altieri Barbara , Ronchi Cristina L 
Published: February 2025

Abstract

Context
Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy with difficult to predict clinical outcomes. The S-GRAS score combines clinical and histopathological variables (tumor stage, grade, resection status, age, and symptoms) and showed good prognostic performance for patients with ACC.

Objective
To improve ACC prognostic classification by applying robust machine learning (ML) models.

Method
We developed ML models to enhance outcome prediction using the published S-GRAS dataset (n = 942) as the training cohort and an independent dataset (n = 152) for validation. Sixteen ML models were constructed based on individual clinical variables. The best-performing models were used to develop a web-based tool for individualized risk prediction.

Results
Quadratic Discriminant Analysis, Light Gradient Boosting Machine, and AdaBoost Classifier models exhibited the highest performance, predicting 5-year overall mortality (OM), and 1-year and 3-year disease progression (DP) with F1 scores of 0.79, 0.63, and 0.83 in the training cohort, and 0.72, 0.60, and 0.83 in the validation cohort. Sensitivity and specificity for 5-year OM were at 77% and 77% in the training cohort, and 65% and 81% in the validation cohort, respectively. A web-based tool (https://acc-survival.streamlit.app) was developed for easily applicable and individualized risk prediction of mortality and disease progression.

Conclusion
S-GRAS parameters can efficiently predict outcome in patients with ACC, even using a robust ML model approach. Our web app instantly estimates the mortality and disease progression for patients with ACC, representing an accessible tool to drive personalized management decisions in clinical practice.
Dual Sourcing Under Internal and External Volatilities
Authors: Federgruen Awi , Liu Zhe , Lu Jiaqi 
Published: February 2025

Problem definition: We study a dual sourcing problem in an increasingly volatile world. We consider two types of volatilities. External volatilities reflect fluctuating economic conditions via an underlying Markov-modulated state-of-the-world that affects the two suppliers’ cost structures, capacity limits, supply mechanisms, and demands. Internal volatilities affect the actual outputs resulting from random supply processes. Demand distributions are impacted by both types of volatilities. Methodology/results: We show how the optimal combined ordering strategy from the two suppliers, along with a salvaging policy, can be efficiently computed under the conventional assumption of consecutive lead times. We characterize the relatively simple structure of the optimal policies and systematically compare the two types of volatilities. Managerial implications: By exploiting dual sourcing options, we find that the firm can benefit from external volatilities; indeed, benefits increase as volatilities increase in specific ways. Numerical studies illustrate these results and reject other reasonable conjectures. Funding: This work was supported by the Guangdong Key Lab of Mathematical Foundations for Artificial Intelligence and the National Natural Science Foundation of China [Grants 72192805 and 72401245]. Supplemental Material: The online appendices are available at https://doi.org/10.1287/msom.2024.0987 .
Effects of initial foot position on neuromuscular and biomechanical control during the stand-to-sit movement: Implications for rehabilitation strategies
Authors: Jeon Woohyoung , Dalby Ashley , Dong Xuanliang Neil , Goh Chung-Hyun 
Published: February 2025

Background
Initial foot position (IFP) is one of the important movement strategies that influence neuromuscular and biomechanical control during sit-to-stand (STS) movements. Similarly, stand-to-sit (StandTS) is vital in rehabilitation settings for evaluating strength and balance control during descending movements. Understanding how IFP impacts changes in biomechanical and neuromuscular movement control factors during StandTS can provide valuable insights for designing effective rehabilitation programs.

Methods
Twelve healthy young adults participated in this study, examining three symmetric IFPs: (1) REF (reference); (2) wide: each foot was shifted outwards by 30% from REF; (3) TO (toes-out): symmetric toes-out angle of 30° from REF. Kinematic and kinetic differences among the three IFPs during StandTS were analyzed, along with the characteristics of muscle activation patterns using muscle synergy analysis.

Results
In the wide IFP, trunk flexion angle was reduced, and valgus angle was greater than in the other IFPs. The TO IFP resulted in greater dorsiflexion and knee flexion angles compared to the REF and wide IFPs. Compared to the REF IFP, both wide and TO IFPs showed greater eccentric work at the hip joint in the anterior-posterior (power absorption) and the vertical direction (gravitational force control) and demonstrated reduced postural sway in medio-lateral and vertical directions. Muscle synergy analysis of EMG activity revealed increased activation of back and plantar flexor muscle in the wide IFP, and increased contribution of hip joint muscles in the TO IFP.

Conclusion
The wide IFP increased the valgus angle, leading to reduced trunk flexion with increased back muscle activation. The TO IFP enabled greater angular displacement at the ankle and knee joints, enhancing hip joint muscle involvement in StandTS movement control. Both the wide and TO IFPs facilitated hip joint work, improving postural sway control during the descent phase of StandTS. These findings provide valuable insights for designing rehabilitation strategies tailored to specific patient needs.
miR-455-3p has superior diagnostic potential to PSA in peripheral blood for prostate cancer
Authors: Cen Yi , Feng Shourui , Xu Yuyu , Zhang Churuo , Lin Xiangjin , Ye Xuan , Zha Zeyu , Wang Haiyan , Zhu Guangbin 
Published: February 2025

Background
Prostate-specific antigen (PSA) is commonly used as a biomarker to diagnose and predict the course of prostate cancer (PCa). However, PSA detection is susceptible to changes in the physiologic environment, which may lead to some misdiagnosis. Thus, it is crucial to find a novel diagnostic marker.

Methods
We accessed microRNA (miRNA) expression datasets (GSE206793 and GSE112264) from the GEO database, analyzing peripheral blood samples from PCa patients. Differentially expressed miRNAs (DEmiRNAs) were identified using GEO2R. A specific miRNA, miR-455-3p, was pinpointed through rigorous analysis of clinical correlations and ROC curves. Peripheral blood samples from healthy individuals and PCa patients were subjected to qRT-PCR validation, aligning results with the GSE206793 dataset. The miRWalk database was utilized to predict downstream genes, while STRING facilitated the construction of a protein-protein interaction (PPI) network. KEGG pathway analysis enriched our understanding of potential molecular pathways.

Results
We found that miR-455-3p was highly expressed in the peripheral blood of PCa patients with Gleason score (GS) ≥ 8, while independent of T stage, age and PSA. ROC analysis revealed a favorable diagnostic efficacy of miR-455-3p and AUC for the two datasets was respectively 0.943 and 0.847. The qRT-PCR assay also revealed consistent results. Interestingly, the PSA levels of P1 (GS = 5 + 4) and P6 (GS = 3 + 3) were respectively 3.38 and 4.45 ng/ml, while miR-455-3p was highly expressed in both, suggesting its low misdiagnosis. The speculation was validated in GSE206793 dataset. Finally, 9 potential targets of miR-455-3p were predicted. PPI network revealed PPP2R2A, ITGB1 and CDKN1A as key nodes. KEGG pathway analysis revealed that they were enriched in various cancers, biological processes and molecular signals.

Conclusion
Our study identifies miR-455-3p as a promising diagnostic marker for PCa, outperforming PSA in terms of specificity and sensitivity. The robustness of miR-455-3p, coupled with its potential downstream targets and associated pathways, highlights its clinical significance for improved PCa diagnosis and management.
Notch2/3-DLL4 interaction in urothelial cancer cell lines supports a tumorigenic role of Notch signaling pathways in bladder carcinoma
Authors: Zhang Chuan , Weimann Annett , Stolzenburg Jens-Uwe , Neuhaus Jochen , Berndt-Paetz Mandy 
Published: February 2025

Introduction
The Notch pathway plays an important role in many aspects of cancer biology and acts in a dichotomous way in bladder cancer. The mechanisms behind this behavior are still elusive. Here, we analyzed DLL4 and Notch receptor expression, interaction and downstream signaling in human bladder cancer cells.

Materials and methods
The expression levels of Notch pathway components (Notch1-4, DLL4, HES1, HEY1) were assessed in papillary (G1: RT-4) and non-papillary bladder cancer cell lines (G2-G4: RT-112, 647-V, T-24, KU-19-19, CAL-29) by qRT-PCR and immunofluorescence. Expression data were validated by analyzing data from open-source databases (CCLE; TCGA). The endogeneous interactions of Notch2/Notch3 receptors and the ligand DLL4 were studied by in situ proximity ligation assay. Activation of canonical Notch signaling was evaluated by stimulation with recombinant DLL4 protein.

Results
All Notch targets were expressed, with Notch2 and Notch3 showing the highest expression levels. Endogeneous interactions between Notch2/3 and DLL4 were detected in all BCa cell lines. Amounts of Notch2/3-DLL4 complexes were high in RT-112 and CAL-29, while RT-4/647-V showed moderate and T-24, KU-19-19 low abundance. Proportion of (peri-) nuclear interaction complexes correlated negatively with Notch downstream targets. DLL4 stimulation resulted in canonical Notch pathway activation and increased tumor cell viability and proliferation in RT-4, 647-V, T-24 and KU-19-19 cells.

Discussion
The Notch signaling pathway can discriminate between different receptors and may play an essential role in the progression of bladder carcinoma. We demonstrated for the first time direct interactions between DLL4 and Notch2/3 associated to activation of canonical downstream Notch signaling and increased tumor cell behavior in human bladder cancer cells. Our data support the view that the Notch2/3-DLL4 axis plays an oncogenic role in bladder cancer. Further analyses of Notch signaling in bladder cancer can promote the development of tailored anti-DLL4/Notch bladder cancer therapies in the future.
Photogrammetric approach to detect road pavement friction
Authors: Svatý Zdeneˇk , Vrtal Pavel , Shults Roman , Kohout Tomáš , Nouzovský Luboš , Blodek Tomáš , Kocián Karel 
Published: February 2025

This paper deals with evaluation of photogrammetric measurements of pavement macrotexture for the purposes of new non-contact method for determination of pavement skid resistance. The aim was to create a method that yields results comparable to existing pavement friction measurement techniques, particularly the sand method, and to assess whether the measurements obtained using the non-contact approach are equally effective. Additionally, the goal was to introduce and define limits for camera calibration applicable to similar cases of object measurements at close distances. Based on existing standards, specific pavement samples exhibiting various macrotexture qualities were selected. The authors conducted 23 different combinations of photogrammetric measurements based on their findings during the evaluations. A comparison of the applied procedures with a reference measurement using the sand method was made, and the measurement error rate was calculated. By evaluating the different variations of the road surface models created, it was concluded that the most reliable results for defining friction are obtained by interleaving the test specimen through a plane based on the principle of best fit using the four highest points of the macrotexture. The ideal size of the sub-areas for applying the mask is 7.5–10 mm. Photogrammetry has proven to be a suitable and accurate tool for assessing pavement surface texture and can be considered as a suitable alternative to other skid resistance measurement approaches.
Global burden of thyroid cancer in adolescents and young adults (aged 15–39 years) from 1990 to 2021: A systematic analysis of the Global Burden of Disease Study 2021
Authors: Qiu Zijian , Yu Shengjian , Zheng Lin , Lou Ying , Chen Xiuxia , Xuan Feng 
Published: February 2025

Background
Thyroid cancer (TC) is the most common malignancy of the endocrine system and head-and-neck region, yet data on its burden in adolescents and young adults (AYAs) is lacking. This study aimed to estimate the global burden of TC among AYAs from 1990 to 2021.

Methods
Utilizing the Global Burden of Disease (GBD) 2021 data, we analyzed age-standardized rates of incidence, prevalence, and disability-adjusted life-years (DALYs) on global, regional, and national scales. Joinpoint regression was employed to determine average annual percentage change (AAPC), with frontier analysis revealing regions for improvement. Decomposition analysis assessed the impacts of population aging, growth, and epidemiological changes. Projections for disease burden extending to 2040 were generated using the Bayesian Age-Period-Cohort model.

Result
In 2021, there were 48.2 thousand incident cases, 436.1 thousand prevalent cases, and 183.5 thousand DALYs worldwide. Meantime, the age-standardized incidence rates (ASIR), age-standardized prevalence rates (ASPR), and age-standardized DALYs rates (ASDR) were 1.6, 14.3 and 6.1 per 100 000, respectively. From 1990 to 2021, the ASIR, ASPR and ASDR increased with AAPCs of 1.73, 1.77, and 0.38, respectively. Socio-demographic resources in Saudi Arabia, Taiwan (Province of China), Iceland, United Arab Emirates, and United States Virgin Islands have the potential to lower ASDR due to TC among AYAs. Furthermore, 13.3 thousand and 34.9 thousand new cases occurred in the males and females in 2021. Among 5 age groups, the highest numbers of incidence, prevalence, and DALYs, along with ASRs, were observed in the 35–39 age group. Global projections indicated a continuous rise in numbers of incidence, prevalence, and DALYs, with estimates of 60.2 thousand, 558.4 thousand, and 199.7 thousand by 2040, respectively.

Conclusion
The global burden of TC among AYAs was on the rise, with significant disparities by regions, genders, and age groups, highlighting the necessity for targeted and effective interventions.
A subnational socioeconomic assessment of family planning levels, projections, and disparities among married women of reproductive age in Cameroon
Authors: Nsashiyi Raïssa Shiyghan , Rahman Md Mizanur , Ndam Lawrence Monah , Hashizume Masahiro 
Published: February 2025

Background
Local-level socioeconomic gradients significantly influence access to reproductive health services in developing countries. This study examines disparities in family planning use among married women of reproductive age across Cameroon’s subnational territories, highlighting inequities often overlooked in national analyses. Furthermore, it incorporates HIV status (a key yet frequently omitted covariate) into the assessment of family planning determinants.

Methods
A Bayesian hierarchical model incorporated with Cameroon Demographic and Health Survey cross-sectional data (between 1991 and 2018) was employed to generate estimates of family planning indicators per residence, wealth, and education categories within each region. Slope index of inequality was used to quantify disparities. The determinants analysis involved Bayesian logistic regression.

Results
Estimates for 2023 revealed that the Centre region’s urban and rural areas had the highest modern contraceptive prevalence rate overall, with 49.0% (24.9–73.8) and 28.2% (12.4–52.3), respectively. The rural Far North had the least estimate [3.9% (1.5–10.5)]. Demand satisfied with modern methods was highest among Adamawa region’s richest quintile [82.9% (58.1 to 94.4)] and higher educated [85.9% (69.5 to 94.2)], and lowest among the East region’s poorest [5.3% (1.5 to 16.5)] and Far North’s none-educated [8.6% (3.3 to 20.4)]. Unmet need for modern methods was lowest among the West region’s richest [5.1% (1.8 to 13.5)] and highest among the Littoral’s poorest [23.1% (9.4 to 47.4)]. 2030 projections show the widest wealth- and education-based gaps for demand satisfied with modern methods in the Adamawa [27.0 percentage points (%p) (2.3 to 51.6) and 79.3%p (73.9 to 84.7), respectively]. Age ≥  20 years, higher education level, practising Catholic/Christian religion, having ≥  one living child(ren), and higher household wealth quintile, were associated with increased odds of modern contraceptive use.

Conclusion
Increased focus is essential on rural, poorer, and less educated populations, particularly in the Northern regions, to effectively address family planning inequities across Cameroon.
Specialised palliative care in nursing homes – Retrospective analysis on the basis of claims data
Authors: Rehner Laura , Moon Kilson , Hoffmann Wolfgang , van den Berg Neeltje 
Published: February 2025

Background
The aim of palliative care is to improve the quality of life of patients with a life limiting illness. In Germany, nursing homes are increasingly the last residence and a common place of death for older people. This renders these institutions as places with a high need for palliative care. However, the frequency of specialised palliative care services in nursing homes in Germany is often low.

Objectives
The aim of this study is 1) to analyse the types and frequencies of services provided by specialised ambulatory palliative care teams in nursing homes in the German federal state of Mecklenburg-Western Pomerania, and 2) to examine whether the frequency of specialised palliative services in nursing homes is comparable to patients living in their private homes.

Methods
The analysis was based on data of the association of statutory health insurance physicians Mecklenburg-Western Pomerania (Germany), data of the statutory health insurance BARMER, and population data. All patients who received specialised ambulatory palliative care in nursing homes in the years 2015–2017 were included in the analysis. For the comparison of the utilisation of specialised ambulatory palliative care in nursing homes with patients in private households, two comparable groups were created using claims, population data and life-year-mortality tables of the general population. It was assumed that people ≥80 years with a life expectancy of <12 months were potential candidates for the utilisation of palliative care. Data were analysed using descriptive statistics and Chi-Square tests.

Results
In Mecklenburg-Western Pomerania, 6,096 patients received specialised ambulatory palliative care in the time period 2015 to 2017. Of these, 16.0% (n = 978) were nursing home residents. The median duration of specialised ambulatory palliative care in nursing homes was 12.0 days, for people in private households 27.2 days. The rate of patients receiving specialised ambulatory palliative care in nursing homes was 4.7%, for people in the comparable group in private households it was 9.2% (p < 0.0001).

Conclusion
Only a small number of nursing home residents received specialised ambulatory palliative care in their last year of life. The rate among those living in their own homes is about twice as high. The results indicate that nursing home residents may have less access to specialised ambulatory palliative care than patients living in private households. Specialised ambulatory palliative care services provision in nursing homes should be improved.
Contemporary Landscape of Medical Technology in Gastroenterology Between 2013 and 2023
Authors: Hennessey Megan M. , Xue Shan , Strigenz Rebecca Z. , Bagley Pamela , Shah Eric D. 
Published: February 2025

ABSTRACT
Medical technology in gastroenterology spans devices, point-of-care diagnostics, digital health and artificial intelligence. We conducted a narrative review of US Food and Drug Administration-reviewed medical technology on the available evidence base to support uptake in clinical practice. 713 new GI devices were FDA-approved or cleared between 2013 and 2023. The most frequent technologies had indications for use in general endoscopy (442 or 62.0% of all new technologies) with advanced endoscopy technologies being the second most common (172 or 24.1%). Ninety-nine new technologies had indications for use outside of the endoscopy suite. 99% of new technologies were FDA-cleared against existing technologies via the 510(k) pathway rather than approved on new clinical data. Among the 19 devices with clinical trial data, trials were limited in sample size and generally evaluated disease-related changes or technical success rather than patient-reported outcomes that anchor drug trials. Twelve devices (63.2%) had fsavorable, published cost-effective data. To promote evidence-based discussion and uptake of new technology, and especially disruptive or high-risk technology, we propose a practical framework informed by balancing probable efficacy and safety and considering cost-effectiveness.
The Value of Mere Willing: Revisiting Kant’s Argument for the Formula of the End in Itself
Authors: Bailey Tom 
Published: February 2025

Abstract
In this article I attempt to explain Kant’s notoriously obscure argument for the principle that every rational being should be treated as an “end,” and not merely as a means. I take my lead from the appearance in the argument of terms and ideas that he uses earlier in the Groundwork to express two distinctive features of moral value and to make a related claim about how moral value is achieved. I argue that, of the candidates for the “end” of moral action that Kant considers, only rational beings instantiate both of these features and satisfy the related claim. I also argue that these features and this claim explain why no other candidates need be considered and why moral actions must have an “end” at all. Thus I show that these features and this claim resolve the puzzles posed by Kant’s own argument and make sense of some of the remarks that he makes in it.