bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modelling cost-effectiveness of replacement strategies for ambulance services in the Ministry of Health Malaysia
Authors: Mohd Hassan Nor Zam Azihan , Bahari Mohd Shahri , Raman Sivaraj , Aminuddin Farhana , Mohd Nor Sham Kunusagaran Mohd Shaiful Jefri , Zaimi Nur Amalina , Wong Min Fui , Mostapha Marhaini , Mohamad Nor Ahmad Tajuddin , Shahari Mohd Ridzwan 
Published: February 2024

Abstract
Background
Emergency Medical Service (EMS) is a very crucial aspect of the healthcare system in providing urgent management and transportation of patients during emergencies. The sustainability of the services is however greatly impacted by the quality and age of ambulances. While this has led to numerous replacement policy recommendations, the implementations are often limited due to a lack of evidence and financial constraints. This study thus aims to develop a cost-effectiveness model and testing the model by evaluating the cost-effectiveness of 10-year and 15-year compulsory ambulance replacement strategies in public healthcare for the Malaysian Ministry of Health (MOH).

Methods
A Markov model was developed to estimate the cost and outcomes ambulance replacement strategies over a period of 20 years. The model was tested using two alternative strategies of 10-year and 15-year. Model inputs were derived from published literature and local study. Model development and economic analysis were accomplished using Microsoft Excel 2016. The outcomes generated were costs per year, the number of missed trips and the number of lives saved, in addition to the Incremental Cost-Effectiveness Ratio (ICER). One-Way Deterministic Sensitivity Analysis (DSA) and Probabilistic Sensitivity Analysis (PSA) were conducted to identify the key drivers and to assess the robustness of the model.

Results
Findings showed that the most expensive strategy, which is the implementation of 10 years replacement strategy was more cost-effective than 15 years ambulance replacement strategy, with an ICER of MYR 11,276.61 per life saved. While an additional MYR 13.0 million would be incurred by switching from a 15- to 10-year replacement strategy, this would result in 1,157 deaths averted or additional live saved per year. Sensitivity analysis showed that the utilization of ambulances and the mortality rate of cases unattended by ambulances were the key drivers for the cost-effectiveness of the replacement strategies.

Conclusions
The cost-effectiveness model developed suggests that an ambulance replacement strategy of every 10 years should be considered by the MOH in planning sustainable EMS. While this model may have its own limitation and may require some modifications to suit the local context, it can be used as a guide for future economic evaluations of ambulance replacement strategies and further exploration of alternative solutions.
Circular RNAs and their roles in idiopathic pulmonary fibrosis
Authors: Surendran Akshaya , Huang Chaoqun , Liu Lin 
Published: February 2024

AbstractIdiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease with limited treatment options. Circular RNAs (circRNAs) have emerged as a novel class of non-coding RNAs with diverse functions in cellular processes. This review paper aims to explore the potential involvement of circRNAs in the pathogenesis of IPF and their diagnostic and therapeutic implications. We begin by providing an overview of the epidemiology and risk factors associated with IPF, followed by a discussion of the pathophysiology underlying this complex disease. Subsequently, we delve into the history, types, biogenesis, and functions of circRNAs and then emphasize their regulatory roles in the pathogenesis of IPF. Furthermore, we examine the current methodologies for detecting circRNAs and explore their diagnostic applications in IPF. Finally, we discuss the potential utility of circRNAs in the treatment of IPF. In conclusion, circRNAs hold great promise as novel biomarkers and therapeutic targets in the management of IPF.
CD47—a novel prognostic predicator in epithelial ovarian cancer and correlations with clinicopathological and gene mutation features
Authors: Luo Xukai , Mo Jiahang , Zhang Min , Huang Wu , Bao Yiting , Zou Ruoyao , Yao Liangqing , Yuan Lei 
Published: February 2024

Abstract
Background
Epithelial ovarian cancer (EOC) is insensitive to immunotherapy due to its poor immunogenicity; thus, suitable biomarkers need to be identified for better prognostic stratification and individualized treatment. CD47 is a novel immunotherapy target; however, its impact on EOC prognosis is controversial and correlation with genetic features is unclear. The aim of this study was to investigate the prognostic significance of CD47 and its correlations with biological behaviors and genetic features of EOC.

Methods
Immunohistochemistry (IHC) and next-generation sequencing (NGS) were performed to examine expressions of CD47, PD-L1, and genomic mutations in the tissue samples of 75 EOC patients. Various clinicopathologic and genomic features were then evaluated to determine their correlation with CD47 expression. Kaplan–Meier analysis and Cox regression analysis were used to identify independent prognostic factors. Risk score modeling was then established, and the predictive capacity of this model was further confirmed by nomogram analysis.

Results
CD47 was mainly expressed in the tumor cell membrane and cytoplasm, and the rate of high CD47 expression was 63.7%. CD47 expression was associated with various clinicopathological factors, including FIGO stage, CA125 and HE4 value, presence of multidisciplinary surgeries, presence and volume of ascites, lymph-node metastasis, Ki-67 index and platinum-resistant, as well as genetic characteristics like BRCA mutation, HRD status, and TP53 mutation in EOC. Patients with high CD47 expression showed worse prognosis than the low-expression group. Cox regression analysis demonstrated that CA125, CD47, and BRCA mutation were independent factors for EOC prognosis. Patients were then categorized into high-risk and low-risk subgroups based on the risk score of the aforementioned independent factors, and the prognosis of the high-risk group was worse than those of the low-risk group. The nomogram showed adequate discrimination with a concordance index of 0.777 (95% CI, 0.732–0.822). The calibration curve showed good consistency.

Conclusion
CD47 correlated with various malignant biology and genetic characteristics of EOC and may play pivotal and multifaceted roles in the tumor microenvironment of EOC Finally, we constructed a reliable prediction model centered on CD47 and integrated CA125 and BRCA to better guide high-risk population management.
Algorithm-assisted diagnosis of Hirschsprung’s disease – evaluation of robustness and comparative image analysis on data from various labs and slide scanners
Authors: Greenberg Ariel , Samueli Benzion , Farkash Shai , Zohar Yaniv , Ish-Shalom Shahar , Hagege Rami R. , Hershkovitz Dov 
Published: February 2024

Abstract
Background
Differences in the preparation, staining and scanning of digital pathology slides create significant pre-analytic variability. Algorithm-assisted tools must be able to contend with this variability in order to be applicable in clinical practice. In a previous study, a decision support algorithm was developed to assist in the diagnosis of Hirschsprung's disease. In the current study, we tested the robustness of this algorithm while assessing for pre-analytic factors which may affect its performance.

Methods
The decision support algorithm was used on digital pathology slides obtained from four different medical centers (A-D) and scanned by three different scanner models (by Philips, Hamamatsu and 3DHISTECH). A total of 192 cases and 1782 slides were used in this study. RGB histograms were constructed to compare images from the various medical centers and scanner models and highlight the differences in color and contrast.

Results
The algorithm was able to correctly identify ganglion cells in 99.2% of cases, from all medical centers (All scanned by the Philips slide scanner) as well as 95.5% and 100% of the slides scanned by the 3DHISTECH and Hamamatsu brand slide scanners, respectively. The total error rate for center D was lower than the other medical centers (3.9% vs 7.1%, 10.8% and 6% for centers A-C, respectively), the vast majority of errors being false positives (3.45% vs 0.45% false negatives). The other medical centers showed a higher rate of false negatives in relation to false positives (6.81% vs 0.29%, 9.8% vs 1.2% and 5.37% vs 0.63% for centers A-C, respectively). The total error rates for the Philips, Hamamatsu and 3DHISTECH brand scanners were 3.9%, 3.2% and 9.8%, respectively. RGB histograms demonstrated significant differences in pixel value distribution between the four medical centers, as well as between the 3DHISTECH brand scanner when compared to the Philips and Hamamatsu brand scanners.

Conclusions
The results reported in this paper suggest that the algorithm-based decision support system has sufficient robustness to be applicable for clinical practice. In addition, the novel method used in its development – Hierarchial-Contexual Analysis (HCA) may be applicable to the development of algorithm-assisted tools in other diseases, for which available datasets are limited. Validation of any given algorithm-assisted support system should nonetheless include data from as many medical centers and scanner models as possible.
Global exact optimisations for chloroplast structural haplotype scaffolding
Authors: Epain Victor , Andonov Rumen 
Published: February 2024

Abstract
Background
Scaffolding is an intermediate stage of fragment assembly. It consists in orienting and ordering the contigs obtained by the assembly of the sequencing reads. In the general case, the problem has been largely studied with the use of distances data between the contigs. Here we focus on a dedicated scaffolding for the chloroplast genomes. As these genomes are small, circular and with few specific repeats, numerous approaches have been proposed to assemble them. However, their specificities have not been sufficiently exploited.

Results
We give a new formulation for the scaffolding in the case of chloroplast genomes as a discrete optimisation problem, that we prove the decision version to be $$\mathcal{NP}$$
NP
-Complete. We take advantage of the knowledge of chloroplast genomes and succeed in expressing the relationships between a few specific genomic repeats in mathematical constraints. Our approach is independent of the distances and adopts a genomic regions view, with the priority on scaffolding the repeats first. In this way, we encode the structural haplotype issue in order to retrieve several genome forms that coexist in the same chloroplast cell. To solve exactly the optimisation problem, we develop an integer linear program that we implement in Python3 package khloraascaf. We test it on synthetic data to investigate its performance behaviour and its robustness against several chosen difficulties.

Conclusions
We succeed to model biological knowledge on genomic structures to scaffold chloroplast genomes. Our results suggest that modelling genomic regions is sufficient for scaffolding repeats and is suitable for finding several solutions corresponding to several genome forms.
Combined Systemic Immune-inflammatory Index (SII) and Geriatric Nutritional Risk Index (GNRI) predict survival in elderly patients with hip fractures: a retrospective study
Authors: Zhou Ling , Huang Chao , Zhu Xianjie , Ma Zhenhua 
Published: February 2024

Abstract
Purpose
The Systemic Immune-inflammatory Index (SII) and Geriatric Nutritional Risk Index (GNRI) have undergone comprehensive examination and validation in forecasting the outcomes of diverse medical conditions. Nevertheless, the correlation between the combined use of GNRI and SII metrics and hip fractures has yet to be elucidated. This study aimed to determine whether the amalgamation of SII and GNRI scores constitutes an independent prognostic factor for elderly patients with hip fractures.

Methods
We conducted a retrospective analysis of elderly patients admitted to our facility with hip fractures, encompassing both femoral neck and intertrochanteric fractures. Demographic information, experimental parameters, and postoperative complications were systematically recorded. The Geriatric Nutritional Risk Index (GNRI) and Systemic Immunoinflammatory Index (SII) were meticulously computed. Receiver operating characteristic (ROC) curves were generated, and optimal cutoff values for each parameter were determined. Subsequently, a multivariate Cox regression analysis was employed to assess the predictive utility of the SII–GNRI score in relation to 1-year postoperative mortality among elderly patients with hip fractures.

Results
In a study involving 597 patients, 90 of whom experienced mortality within 1 year, it was observed that the SII-GNRI score in the group of patients who passed away was significantly higher compared to the group that survived. Following a multifactorial adjustment, it was established that a high SII–GNRI score served as an independent predictor of 1-year all-cause mortality in older patients with hip fractures. In addition to the SII–GNRI score, factors such as length of hospital stay, CCI > 2, and blood transfusion were also identified as independent risk factors for survival. Notably, the incidence of postoperative complications in patients with high SII–GNRI scores was significantly greater than in patients with low scores.

Conclusion
The SII–GNRI score proves valuable in predicting the 1-year survival rate for elderly patients with hip fractures who have undergone surgery.
Rare subclonal sequencing of breast cancers indicates putative metastatic driver mutations are predominately acquired after dissemination
Authors: Lawrence-Paul Matthew R. , Pan Tien-chi , Pant Dhruv K. , Shih Natalie N. C. , Chen Yan , Belka George K. , Feldman Michael , DeMichele Angela , Chodosh Lewis A. 
Published: February 2024

Abstract
Background
Evolutionary models of breast cancer progression differ on the extent to which metastatic potential is pre-encoded within primary tumors. Although metastatic recurrences often harbor putative driver mutations that are not detected in their antecedent primary tumor using standard sequencing technologies, whether these mutations were acquired before or after dissemination remains unclear.

Methods
To ascertain whether putative metastatic driver mutations initially deemed specific to the metastasis by whole exome sequencing were, in actuality, present within rare ancestral subclones of the primary tumors from which they arose, we employed error-controlled ultra-deep sequencing (UDS-UMI) coupled with FFPE artifact mitigation by uracil-DNA glycosylase (UDG) to assess the presence of 132 “metastasis-specific” mutations within antecedent primary tumors from 21 patients. Maximum mutation detection sensitivity was ~1% of primary tumor cells. A conceptual framework was developed to estimate relative likelihoods of alternative models of mutation acquisition.

Results
The ancestral primary tumor subclone responsible for seeding the metastasis was identified in 29% of patients, implicating several putative drivers in metastatic seeding including LRP5 A65V and PEAK1 K140Q. Despite this, 93% of metastasis-specific mutations in putative metastatic driver genes remained undetected within primary tumors, as did 96% of metastasis-specific mutations in known breast cancer drivers, including ERRB2 V777L, ESR1 D538G, and AKT1 D323H. Strikingly, even in those cases in which the rare ancestral subclone was identified, 87% of metastasis-specific putative driver mutations remained undetected. Modeling indicated that the sequential acquisition of multiple metastasis-specific driver or passenger mutations within the same rare subclonal lineage of the primary tumor was highly improbable.

Conclusions
Our results strongly suggest that metastatic driver mutations are sequentially acquired and selected within the same clonal lineage both before, but more commonly after, dissemination from the primary tumor, and that these mutations are biologically consequential. Despite inherent limitations in sampling archival primary tumors, our findings indicate that tumor cells in most patients continue to undergo clinically relevant genomic evolution after their dissemination from the primary tumor. This provides further evidence that metastatic recurrence is a multi-step, mutation-driven process that extends beyond primary tumor dissemination and underscores the importance of longitudinal tumor assessment to help guide clinical decisions.
AdductHunter: identifying protein-metal complex adducts in mass spectra
Authors: Long Derek , Eade Liam , Sullivan Matthew P. , Dost Katharina , Meier-Menches Samuel M. , Goldstone David C. , Hartinger Christian G. , Wicker Jörg S. , Taškova Katerina 
Published: February 2024

AbstractMass spectrometry (MS) is an analytical technique for molecule identification that can be used for investigating protein-metal complex interactions. Once the MS data is collected, the mass spectra are usually interpreted manually to identify the adducts formed as a result of the interactions between proteins and metal-based species. However, with increasing resolution, dataset size, and species complexity, the time required to identify adducts and the error-prone nature of manual assignment have become limiting factors in MS analysis. AdductHunter is a open-source web-based analysis tool that automates the peak identification process using constraint integer optimization to find feasible combinations of protein and fragments, and dynamic time warping to calculate the dissimilarity between the theoretical isotope pattern of a species and its experimental isotope peak distribution. Empirical evaluation on a collection of 22 unique MS datasetsshows fast and accurate identification of protein-metal complex adducts in deconvoluted mass spectra.
Estimation of lifetime productivity loss from patients with chronic diseases: methods and empirical evidence of end-stage kidney disease from Taiwan
Authors: Wang Fuhmei , Hwang Jing-Shiang , Huang Wen-Yen , Chang Yu-Tzu , Wang Jung-Der 
Published: February 2024

Abstract
Objective
Studies that examine the broad allocation of resources, regardless of who bears the costs, should ideally estimate costs from a societal perspective. We have successfully integrated survival rates, employment ratios, and earnings to address the significant challenge of evaluating societal value through productivity assessments of patients with end-stage kidney disease (ESKD) in Taiwan.

Methods
Using a theoretical framework, we interconnected two nationwide databases: the Taiwan National Health Insurance (NHI) and the Taiwan Mortality Registry from 2000 to 2017. Due to the statutory retirement age of 65, we collected data on all patients (83,358) aged 25–64 years diagnosed with ESKD and undergoing maintenance dialysis. We estimated the lifetime survival function through a rolling extrapolation algorithm, which was then combined with the monthly employment ratio and wages to calculate the lifetime employment duration and productivity up to the legal retirement age of ESKD patients. These were compared with sex-, age-, and calendar year-matched referents to determine the loss of employment duration and productivity of ESKD patients.

Results
ESKD patients experienced a loss of approximately 25–56% in lifetime employment duration and a larger loss of about 32–66% in lifetime productivity after adjustments for different age, sex, and calendar year. The annual productivity loss per male (female) ESKD patient relative to that of the age-and calendar year-matched referent ranges from 75.5% to 82.1% (82.3% to 90.3%). During the periods when they are able to work (over the on-the-job duration) male ESKD patients lose between 34 and 56% of their income, and female ESKD patients lose between 39 and 68% of their income, compared to the age-and calendar year-matched referents. The loss of lifetime productivity is a combination of reduced lifetime employment duration, functional disability, absenteeism, and presenteeism at the workplace. The loss related to presenteeism is implied by the reduced wages.

Conclusions
In addition to the loss of employment duration, we have empirically demonstrated the lifetime loss of productivity in patients with ESKD, also indicating the “presenteeism” resulted from inability to perform their job with full capacity over long-term periods.
Graph convolution networks for social media trolls detection use deep feature extraction
Authors: Asif Muhammad , Al-Razgan Muna , Ali Yasser A. , Yunrong Long 
Published: February 2024

AbstractThis study presents a novel approach to identifying trolls and toxic content on social media using deep learning. We developed a machine-learning model capable of detecting toxic images through their embedded text content. Our approach leverages GloVe word embeddings to enhance the model's predictive accuracy. We also utilized Graph Convolutional Networks (GCNs) to effectively analyze the intricate relationships inherent in social media data. The practical implications of our work are significant, despite some limitations in the model's performance. While the model accurately identifies toxic content more than half of the time, it struggles with precision, correctly identifying positive instances less than 50% of the time. Additionally, its ability to detect all positive cases (recall) is limited, capturing only 40% of them. The F1-score, which is a measure of the model's balance between precision and recall, stands at around 0.4, indicating a need for further refinement to enhance its effectiveness. This research offers a promising step towards more effective monitoring and moderation of toxic content on social platforms.