bluuebunny/crossref_metadata_2025_split huggingface dataset:
FMRP-mediated spatial regulation of physiologic NMD targets in neuronal cells
Authors: Kurosaki Tatsuaki , Rambout Xavier , Maquat Lynne E. 
Published: January 2024

AbstractIn non-polarized cells, nonsense-mediated mRNA decay (NMD) generally begins during the translation of newly synthesized mRNAs after the mRNAs are exported to the cytoplasm. Binding of the FMRP translational repressor to UPF1 on NMD targets mainly inhibits NMD. However, in polarized cells like neurons, FMRP additionally localizes mRNAs to cellular projections. Here, we review the literature and evaluate available transcriptomic data to conclude that, in neurons, the translation of physiologic NMD targets bound by FMRP is partially inhibited until the mRNAs localize to projections. There, FMRP displacement in response to signaling induces a burst in protein synthesis followed by rapid mRNA decay.
PICLS with human cells is the first high throughput screening method for identifying novel compounds that extend lifespan
Authors: Alfatah Mohammad , Zhang Yizhong , Naaz Arshia , Cheng Trishia Yi Ning , Eisenhaber Frank 
Published: January 2024

AbstractGerontology research on anti-aging interventions with drugs could be an answer to age-related diseases, aiming at closing the gap between lifespan and healthspan. Here, we present two methods for assaying chronological lifespan in human cells: (1) a version of the classical outgrowth assay with quantitative assessment of surviving cells and (2) a version of the PICLS method (propidium iodide fluorescent-based measurement of cell death). Both methods are fast, simple to conduct, cost-effective, produce quantitative data for further analysis and can be used with diverse human cell lines. Whereas the first method is ideal for validation and testing the post-intervention reproductive potential of surviving cells, the second method has true high-throughput screening potential. The new technologies were validated with known anti-aging compounds (2,5-anhydro-d-mannitol and rapamycin). Using the high-throughput screening method, we screened a library of 162 chemical entities and identified three compounds that extend the longevity of human cells.
Exploring the causal association between rheumatoid arthritis and the risk of cervical cancer: a two-sample Mendelian randomization study
Authors: Xu Minxian , Chen Huan , Tan Tao , Xie Kaihong , Xie Hui , Li Qing 
Published: January 2024

Abstract
Objective
Whether rheumatoid arthritis patients have an increased risk of cervical cancer remains controversial, and further research is needed on this clinical question. This study aims to investigate the association between rheumatoid arthritis and the susceptibility to cervical cancer by employing Mendelian randomization methodology, utilizing the extensive dataset from human genome-wide association data analysis.

Methods
The publicly accessible MR base database was utilized to obtain the complete genome, relevant research findings, and summarized data pertaining to rheumatoid arthritis and cervical cancer. Genetic tool variables, specifically single-nucleotide polymorphisms closely linked to rheumatoid arthritis, were chosen for analysis. Four methods, namely inverse variance weighted analysis, weighted median analysis, weighted mode, and MR-Egger regression, were employed. Statistical analysis was conducted to explore the potential association between rheumatoid arthritis and susceptibility to cervical cancer.

Results
The results of the inverse variance weighted analysis (OR = 1.096, 95% CI: 1.018–1.180, P = 0.015) indicate a significant causal relationship between rheumatoid arthritis and an increased risk of cervical cancer. Furthermore, the absence of horizontal pleiotropic effects (MR-Egger intercept = 0.00025, P = 0.574) and heterogeneity (QEgger = 2.239, I2Egger = 0.225, PEgger = 0.268, QIVW = 2.734, I2IVW = 0.220, PIVW = 0.999) suggests that the observed association is not influenced by confounding factors. Sensitivity analysis and other statistical methods also support the conclusion that genetic pleiotropy does not introduce bias to the findings.

Conclusion
There is a causal relationship between rheumatoid arthritis and the occurrence of cervical cancer. People with rheumatoid arthritis is one of the high-risk groups for early screening of cervical cancer. The IL-18 may play a significant role in elevating the risk of cervical cancer among rheumatoid arthritis patients.
Assessment of lung deformation in patients with idiopathic pulmonary fibrosis with elastic registration technique on pulmonary three-dimensional ultrashort echo time MRI
Authors: Yang Xiaoyan , Yu Pengxin , Sun Haishuang , Deng Mei , Liu Anqi , Li Chen , Meng Wenyan , Xu Wenxiu , Xie Bingbing , Geng Jing , Ren Yanhong , Zhang Rongguo , Liu Min , Dai Huaping 
Published: January 2024

Abstract
Objective
To assess lung deformation in patients with idiopathic pulmonary fibrosis (IPF) using with elastic registration algorithm applied to three-dimensional ultrashort echo time (3D-UTE) MRI and analyze relationship of lung deformation with the severity of IPF.

Methods
Seventy-six patients with IPF (mean age: 62 ± 6 years) and 62 age- and gender-matched healthy controls (mean age: 58 ± 4 years) were prospectively enrolled. End-inspiration and end-expiration images acquired with a single breath-hold 3D-UTE sequence were registered using elastic registration algorithm. Jacobian determinants were calculated from deformation fields and represented on color maps. Jac-mean (absolute value of the log means of Jacobian determinants) and the Dice similarity coefficient (Dice) were compared between different groups.

Results
Compared with healthy controls, the Jac-mean of IPF patients significantly decreased (0.21 ± 0.08 vs. 0.27 ± 0. 07, p < 0.001). Furthermore, the Jac-mean and Dice correlated with the metrics of pulmonary function tests and the composite physiological index. The lung deformation in IPF patients with dyspnea Medical Research Council (MRC) ≥ 3 (Jac-mean: 0.16 ± 0.03; Dice: 0.06 ± 0.02) was significantly lower than MRC1 (Jac-mean: 0. 25 ± 0.03, p < 0.001; Dice: 0.10 ± 0.01, p < 0.001) and MRC 2 (Jac-mean: 0.22 ± 0.11, p = 0.001; Dice: 0.08 ± 0.03, p = 0.006). Meanwhile, Jac-mean and Dice correlated with health-related quality of life, 6 min-walk distance, and the extent of pulmonary fibrosis. Jac-mean correlated with pulmonary vascular-related indexes on high-resolution CT.

Conclusion
The decreased lung deformation in IPF patients correlated with the clinical severity of IPF patients. Elastic registration of inspiratory-to-expiratory 3D UTE MRI may be a new morphological and functional marker for non-radiation and noninvasive evaluation of IPF.

Critical relevance statement
This prospective study demonstrated that lung deformation decreased in idiopathic pulmonary fibrosis (IPF) patients and correlated with the severity of IPF. Elastic registration of inspiratory-to-expiratory three-dimensional ultrashort echo time (3D UTE) MRI may be a new morphological and functional marker for non-radiation and noninvasive evaluation of IPF.

Key points
• Elastic registration of inspiratory-to-expiratory three-dimensional ultrashort echo time (3D UTE) MRI could evaluate lung deformation.
• Lung deformation significantly decreased in idiopathic pulmonary fibrosis (IPF) patients, compared with the healthy controls.
• Reduced lung deformation of IPF patients correlated with worsened pulmonary function and the composite physiological index (CPI).

Graphical Abstract
Updated cranial and mandibular description of the Late Cretaceous (Maastrichtian) baenid turtle Saxochelys gilberti based on micro-computed tomography scans and new information on the holotype-shell association
Authors: Spicher Gaël E. , Lyson Tyler R. , Evers Serjoscha W. 
Published: January 2024

AbstractSaxochelys gilberti is a baenid turtle from the Late Cretaceous Hell Creek Formation of the United States of America known from cranial, shell, and other postcranial material. Baenid turtles are taxonomically diverse and common fossil elements within Late Cretaceous through Eocene faunas. Detailed anatomical knowledge is critical to understanding the systematics and morphological evolution of the group. This is particularly important as baenids represent an important group of continental vertebrates that survived the mass extinction event associated with the Cretaceous/Paleogene boundary. High-resolution micro-computed tomography scanning of the holotype skull reveals additional anatomical details for the already well-known Saxochelys gilberti. This includes the revision of some anatomical statements from the original description, but also detailed knowledge on internal anatomical features of the braincase and the description of a well-preserved axis (cervical vertebra 2). Our new detailed description and previous work on the shell and postcrania make Saxochelys one of the best-described, nearly complete baenid turtles, which are often only known from either isolated shell or cranial material. A revised phylogenetic analysis confirms the position of Saxochelys gilberti as a derived baenid (Eubaeninae) more closely related to Baena arenosa than to Eubaena cephalica.
Cow milk derived-fat inhibits the proliferation of liver cancer-cells
Authors: Ediriweera Meran Keshawa , Cuong Do Manh , Cho Somi Kim 
Published: January 2024

AbstractCow milk is a widely consumed liquid diet, and its fatty acid composition impacts its nutritional and biochemical properties. However, research on the anticancer efficacy of cow milk-derived fat in liver cancer cells is limited. This study investigated the antiproliferative and apoptotic effects of cow milk-derived fat in human hepatoma HepG2 cells. Additionally, the effects of cow milk-derived fat on cell cycle progression and Janus kinase (JAK)-2/signal transducer and activator of transcription (STAT)-3 signaling in HepG2 cells were assessed. Furthermore, the histone deacetylase inhibitory and 2,2-diphenyl-1-picrylhydrazyl radical scavenging potential of cow milk-derived fat were examined. The results demonstrate that cow milk-derived fat can exert antiproliferative and anticlonogenic effects and induce apoptosis in HepG2 cells dose-dependently. Furthermore, cow milk-derived fat induced cell cycle arrest, suppressed the levels of pJAK-2 and pSTAT-3, and inhibited the total histone deacetylase activity in HepG2 cells. The fatty acid profile of cow milk-derived fat revealed that palmitic, oleic, and linoleic acids were abundant as saturated, monounsaturated, and polyunsaturated fatty acids, respectively. Our findings provide a new scientific basis for the development of anticancer strategies that utilize cow milk-derived fat and its derivatives against liver cancer.
Dual-modal radiomics nomogram based on contrast-enhanced ultrasound to improve differential diagnostic accuracy and reduce unnecessary biopsy rate in ACR TI-RADS 4–5 thyroid nodules
Authors: Ren Jia-Yu , Lv Wen-Zhi , Wang Liang , Zhang Wei , Ma Ying-Ying , Huang Yong-Zhen , Peng Yue-Xiang , Lin Jian-Jun , Cui Xin-Wu 
Published: January 2024

Abstract
Background
American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS, TR) 4 and 5 thyroid nodules (TNs) demonstrate much more complicated and overlapping risk characteristics than TR1-3 and have a rather wide range of malignancy possibilities (> 5%), which may cause overdiagnosis or misdiagnosis. This study was designed to establish and validate a dual-modal ultrasound (US) radiomics nomogram integrating B-mode ultrasound (BMUS) and contrast-enhanced ultrasound (CEUS) imaging to improve differential diagnostic accuracy and reduce unnecessary fine needle aspiration biopsy (FNAB) rates in TR 4–5 TNs.

Methods
A retrospective dataset of 312 pathologically confirmed TR4-5 TNs from 269 patients was collected for our study. Data were randomly divided into a training dataset of 219 TNs and a validation dataset of 93 TNs. Radiomics characteristics were derived from the BMUS and CEUS images. After feature reduction, the BMUS and CEUS radiomics scores (Rad-score) were built. A multivariate logistic regression analysis was conducted incorporating both Rad-scores and clinical/US data, and a radiomics nomogram was subsequently developed. The performance of the radiomics nomogram was evaluated using calibration, discrimination, and clinical usefulness, and the unnecessary FNAB rate was also calculated.

Results
BMUS Rad-score, CEUS Rad-score, age, shape, margin, and enhancement direction were significant independent predictors associated with malignant TR4-5 TNs. The radiomics nomogram involving the six variables exhibited excellent calibration and discrimination in the training and validation cohorts, with an AUC of 0.873 (95% CI, 0.821–0.925) and 0.851 (95% CI, 0.764–0.938), respectively. The marked improvements in the net reclassification index and integrated discriminatory improvement suggested that the BMUS and CEUS Rad-scores could be valuable indicators for distinguishing benign from malignant TR4-5 TNs. Decision curve analysis demonstrated that our developed radiomics nomogram was an instrumental tool for clinical decision-making. Using the radiomics nomogram, the unnecessary FNAB rate decreased from 35.3 to 14.5% in the training cohort and from 41.5 to 17.7% in the validation cohorts compared with ACR TI-RADS.

Conclusion
The dual-modal US radiomics nomogram revealed superior discrimination accuracy and considerably decreased unnecessary FNAB rates in benign and malignant TR4-5 TNs. It could guide further examination or treatment options.
Antimicrobial resistance crisis: could artificial intelligence be the solution?
Authors: Liu Guang-Yu , Yu Dan , Fan Mei-Mei , Zhang Xu , Jin Ze-Yu , Tang Christoph , Liu Xiao-Fen 
Published: January 2024

AbstractAntimicrobial resistance is a global public health threat, and the World Health Organization (WHO) has announced a priority list of the most threatening pathogens against which novel antibiotics need to be developed. The discovery and introduction of novel antibiotics are time-consuming and expensive. According to WHO’s report of antibacterial agents in clinical development, only 18 novel antibiotics have been approved since 2014. Therefore, novel antibiotics are critically needed. Artificial intelligence (AI) has been rapidly applied to drug development since its recent technical breakthrough and has dramatically improved the efficiency of the discovery of novel antibiotics. Here, we first summarized recently marketed novel antibiotics, and antibiotic candidates in clinical development. In addition, we systematically reviewed the involvement of AI in antibacterial drug development and utilization, including small molecules, antimicrobial peptides, phage therapy, essential oils, as well as resistance mechanism prediction, and antibiotic stewardship.
Changes of synaptic vesicles in three-dimensional synapse models by treatment with umbelliferone in scopolamine-induced hippocampal injury model
Authors: Choi Ga-Young , Moon Eunyoung , Choi Hyosung , Kweon Hee-Seok 
Published: January 2024

AbstractThe neuroprotective effects of umbelliferone (UMB) were visualized in three-dimensional (3D) images on vesicle density changes of organotypic hippocampal slice tissues (OHSCs) induced by scopolamine by high voltage electron microscopy. Observations revealed that the number of vesicles decreased in OHSCs induced by scopolamine, and UMB was found to inhibit scopolamine-induced reduction in vesicles, resulting in an increase in vesicle count. These 3D models provide valuable insight for understanding the increase of synapse vesicles in hippocampal tissues treated with UMB.
A Neural Separation Algorithm for the Rounded Capacity Inequalities
Authors: Kim Hyeonah , Park Jinkyoo , Kwon Changhyun 
Published: January 2024

The cutting plane method is a key technique for successful branch-and-cut and branch-price-and-cut algorithms that find the exact optimal solutions for various vehicle routing problems (VRPs). Among various cuts, the rounded capacity inequalities (RCIs) are the most fundamental. To generate RCIs, we need to solve the separation problem, whose exact solution takes a long time to obtain; therefore, heuristic methods are widely used. We design a learning-based separation heuristic algorithm with graph coarsening that learns the solutions of the exact separation problem with a graph neural network (GNN), which is trained with small instances of 50 to 100 customers. We embed our separation algorithm within the cutting plane method to find a lower bound for the capacitated VRP (CVRP) with up to 1,000 customers. We compare the performance of our approach with CVRPSEP, a popular separation software package for various cuts used in solving VRPs. Our computational results show that our approach finds better lower bounds than CVRPSEP for large-scale problems with 400 or more customers, whereas CVRPSEP shows strong competency for problems with less than 400 customers. History: Accepted by Andrea Lodi, Area Editor for Design & Analysis of Algorithms–Discrete. Funding: This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) [RS-2023-00259550] and the Institute of Information & Communications Technology Planning & Evaluation (IITP) grant funded by the Korean government (MSIT) [2022-0-01032, Development of Collective Collaboration Intelligence Framework for Internet of Autonomous Things]. Supplemental Material: The online appendix is available at https://doi.org/10.1287/ijoc.2022.0310 .
COMPARISON OF PAIN AND EXTENT OF ANAESTHESIA IN DIGITAL BLOCKS FOR ISOLATED FINGER LACERATIONS: A RANDOMIZED CONTROLLED TRIAL
Authors: Al-Jasim A. , Jarragh A. , Lari A. , Burhamah W. , Alherz M. , Nouri A. , Alshammari Y. , Alrefai S. , Alnusif N. 
Published: January 2024

BackgroundDigital injuries are among the most common presentations to the emergency department. In order to sufficiently examine and manage these injuries, adequate, prompt, and predictable anaesthesia is essential. In this trial, we aim to primarily compare the degree of pain and anaesthesia onset time between the two-injection dorsal block technique (TD) and the single-injection volar subcutaneous block technique (SV). Further, we describe the temporal and anatomical effects of both techniques for an accurate delineation of the anesthetized regions.MethodsA single-centre prospective randomized controlled trial involving patients presenting with isolated wounds to the fingers requiring primary repair under local anaesthesia. Patients were randomized to either the SV or TD blocks. The primary outcome was procedure-related pain (Numerical Rating Scale). Further, we assessed the extent of anaesthesia along with the anaesthesia onset time.ResultsA total of 100 patients were included in the final analysis, 50 on each arm of the study. The median pain score during injection was significantly higher in patients who received TD block than patients who received SV block (median [interquartile range] = 4 [2.25, 5] vs. 3 [2, 4], respectively, P = 0.006). However, anaesthesia onset time was not statistically different among the groups (P = 0.39). The extent of anaesthesia was more predictable in the dorsal block compared to the volar block.ConclusionThe single-injection volar subcutaneous blocks are less painful with a similar anaesthesia onset time. Injuries presenting in the proximal dorsal region may benefit from the two-injection dorsal blocks, given the anatomical differences and timely anaesthesia of the region.
ROLE OF SMARTPHONE APP SYSTEM IN IMPROVING PATIENT EXPERIENCE AND OUTCOMES IN KNEE ARTHROPLASTY
Authors: Mathai N. J. , D'sa P. , Rao P.V. , Chandratreya A. , Kotwal R. 
Published: January 2024

IntroductionWith advances in mobile application, digital health is being increasingly used for remote and personalised care. Patient education, self-management and tele communication is a crucial factor in optimising outcomes.AimsWe explore the use of a smartphone app based orthopaedic care management system to deliver personalised surgical experience, monitor patient engagement and functional outcomes of patients undergoing knee arthroplasty.ResultsOver a 12-month period, 124 patients listed for knee arthroplasty were offered access to the app. Average patient age was 65.4 years (range 49 to 86). 13(10.4%) patients were over 80 years. Compliance with app usage was 86.4%. Compliance with post-operative exercises increased following a message through the app. The mean Oxford knee score improved from a pre-op value of 17 to 35 at a mean follow-up of 6 months. Mean numeric rating scale pain score reduced from 7 pre-operatively to 3 at the latest follow-up. 58 patients (46.7%) used the communication feature on the app (text messages, photos, video consultations), reducing telephone calls and patient foot fall in the hospital. Patient satisfaction with the app was very high.ConclusionWe found the virtual care system to be effective in providing patient education, prehabilitation and post-operative rehabilitation along with being an effective channel of communication between patients and the hospital team. Patient satisfaction and compliance was very high.
Association of a healthy beverage score with total mortality in the adult population of Spain: A nationwide cohort study
Authors: Rodríguez-Ayala Montserrat , Donat-Vargas Carolina , Moreno-Franco Belén , Mérida Diana María , Ramón Banegas José , Rodríguez-Artalejo Fernando , Guallar-Castillón Pilar 
Published: January 2024

Background
Despite the substantial evidence of the relationship between diet and mortality, the role of beverage consumption patterns is not well known. The aim of this study was to assess the association of the adherence to a Healthy Beverage Score (HBS) and all-cause mortality in a representative sample of the Spanish adult population.

Methods and findings
We conducted an observational cohort study using data from the Study on Nutrition and Cardiovascular Risk in Spain (ENRICA), which included 12,161 community-dwelling individuals aged ≥18 years recruited in 2008 to 2010 and followed until January 2022. At baseline, food consumption was collected using a validated diet history. The HBS consists of 7 items, each of which is scored from 1 to 4 (highest adherence). The HBS ranges from 7 to 28 points with a higher score representing a healthier pattern. Adherence was assigned as a higher consumption of low-fat milk, and coffee and tea, a lower consumption of whole-fat milk, no consumption of fruit juice, artificially sweetened beverages, or sugar-sweetened beverages, and no or moderate consumption of alcohol. Total mortality was ascertained by linkage to the Spanish National Death Index. Statistical analyses were performed with Cox models and adjusted for the main confounders, including sociodemographic, lifestyle, dietary variables, and morbidity.
After a mean follow-up of 12.5 years (SD: 1.7; range: 0.5 to 12.9), a total of 967 deaths occurred. For all-cause mortality, the fully adjusted hazard ratio (HR) for the highest versus lowest sex-specific quartiles of HBS was 0.72 (95% confidence interval [0.57, 0.91], p linear-trend = 0.015), corresponding to an 8.3% reduction in the absolute risk of death. A linear relationship between the risk of death and the adherence to the HBS was observed using restricted cubic splines. The results were robust to sensitivity analyses. The main limitation was that repeated measurements on beverage consumption were not available and beverage consumption could have changed during follow-up.

Conclusions
In this study, we observed that higher adherence to the HBS was associated with lower total mortality. Adherence to a healthy beverage pattern could play a role in the prevention of premature mortality.