bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating accuracy in artificial intelligence-powered serial segmentation for sectional images applied to morphological studies with three-dimensional reconstruction
Authors: Muro Satoru , Ibara Takuya , Sugiyama Yuzuki , Nimura Akimoto , Akita Keiichi 
Published: February 2025

Abstract
Three-dimensional (3D) reconstruction is time-consuming owing to segmentation work. We evaluated the accuracy of the artificial intelligence (AI)-based segmentation and tracking model SAM-Track for segmentation of anatomical or histological structures and explored the potential of AI to enhance research efficiency. Images [obtained via computed tomography (CT) and magnetic resonance imaging (MRI)], anatomical sections from a Visible Korean Human open resource, and serial histological section images of cadavers were obtained. Six structures in the CT, MRI, and anatomical sections and seven in the histological sections were segmented using SAM-Track and compared with manual segmentation by calculating the Dice similarity coefficient. Segmented images were then reconstructed three dimensionally. The average Dice scores of CT and MRI results varied (0.13–0.83); anatomical sections showed mostly good accuracy (0.31–0.82). Clear-edged structures, such as the femur and liver, had high scores (0.69–0.83). In contrast, soft tissue structures, such as the rectus femoris and stomach, had variable accuracy (0.38–0.82). Histological sections showed high accuracy, especially for well-delineated tissues, such as the tibia and pancreas (0.95, 0.90). However, the tracking of branching structures, such as arteries and veins, was less successful (0.72, 0.52). In 3D reconstruction, high Dice scores were associated with accurate shapes, whereas low scores indicated discrepancies between the predicted and true shapes. AI-based automatic segmentation using SAM-Track provides moderate-to-good accuracy for anatomical and histological structures and is beneficial for conducting morphological studies involving 3D reconstruction.
Synergistic self-learning approach to establishing individualized treatment rules from multiple benefit outcomes in a calcium supplementation trial
Authors: Zhou Yiwang , Song Peter X K 
Published: February 2025

Abstract
In utero lead exposure poses risks to children’s neurobehavioral development. The Early Life Exposure in Mexico to ENvironmental Toxicants’ calcium supplementation trial studies the effect of calcium supplement in reducing maternal lead exposure to infants during pregnancy. An individualized treatment rule (ITR) is needed to guide pregnant women on taking calcium supplement. This article introduces a statistical learning method, synergistic self-learning (SS-learning), to tackle two challenges in deriving ITR with multiple outcomes, including heterogeneous multidimensional outcomes and complex missing data patterns. Applying SS-learning to the trial, important covariates were identified to form an ITR, expected to lead to higher lead reduction if implemented across the study population.
Correcting for bias due to mismeasured exposure in mediation analysis with a survival outcome
Authors: Cheng Chao , Spiegelman Donna , Li Fan 
Published: February 2025

Abstract
We investigate the impact of exposure measurement error on assessing mediation with a survival outcome modelled by Cox regression. We first derive the bias formulas of natural indirect and direct effects with a rare outcome and no exposure–mediator interaction. We then develop several calibration approaches to correct for the measurement error-induced bias, and generalize our methods to accommodate a common outcome and an exposure–mediator interaction. We apply the proposed methods to analyse the Health Professionals Follow-up Study (1986–2016) and evaluate the extent to which reduced body mass index mediates the protective effect of physical activity on risk of cardiovascular diseases.
Ethylene biosynthesis in legumes: gene identification and expression during early symbiotic stages
Authors: Gómez-Fernández Germán O , van Velzen Robin , Mun Jeong-Hwan , Cook Douglas R , Kohlen Wouter , Larrainzar Estíbaliz 
Published: February 2025

Abstract
The final steps of ethylene biosynthesis involve the consecutive activity of two enzymes, 1-aminocyclopropane-1-carboxylate synthase (ACS) and 1-aminocyclopropane-1-carboxylate oxidase (ACO). These enzymes are encoded by small gene families, which, in the case of legumes, have not been systematically characterized at the level of gene family membership or phylogenetic relationships. Moreover, the absence of consensus nomenclature complicates comparisons within the scientific literature, where authors are addressing the roles of these genes in planta. In this study, we provide a framework in which the ACS and ACO family members of several legume species, including the two model legumes Medicago truncatula and Lotus japonicus, were systematically annotated, named, and analyzed relative to genes from other dicot and monocot model species. A combination of phylogenetic and reciprocal BLAST analyses was used to identify evolutionary relationships among genes, including the identification of orthologous relationships that can inform hypotheses about function. Given the role of ethylene as a negative regulator of the legume-rhizobium symbiosis, we queried publicly available RNA-seq expression datasets to obtain an overview of the expression profiles of these genes in the interaction between M. truncatula and its nitrogen-fixing microsymbiont. The resulting evolutionary framework, as well as structural and expression analyses, are intended to facilitate ongoing functional studies in legumes.
Identification of Urinary Metabolic Biomarkers for H3K27M Mutation Diagnosis in Brainstem Gliomas
Authors: Li Xiaoou , Sun Wei , Guo Zhengguang , Qi Feng , Li Tian , Wang Yujin , Zhang Mingxin , Wang Aiwei , Jiang Zhuang , Xie Luyang , Mai Yiying , Wang Yi , Wu Zhen , Ji Nan , Zhang Yang , Zhang Liwei 
Published: February 2025

Abstract

Background
Brainstem gliomas (BSGs) harboring a histone 3 lysine27-to-methionine (H3K27M) mutation represent one of the deadliest brain tumors with a dismal prognosis, as they exhibit a much worse response to therapy compared to the wildtype BSGs. Early non-invasive recognition of the H3K27M mutation is paramount for clinical decision-making in treating BSGs.

Methods
Plasma and urine samples were prospectively collected from BSG patients before biopsy or surgical resection and were chronologically divided into discovery, test, and validation cohorts. Utilizing the discovery and test cohort samples, an untargeted metabolomic strategy was exploited to identify candidate metabolite biomarkers, related to the H3K27M mutation. The candidate biomarkers were validated in the validation cohort with a targeted metabolomic method.

Results
Differential metabolomic profiles were detected between the H3K27M-mutant and wild-type BSGs in both the plasma and urine, the metabolomic changes were more dramatic in urine than in plasma. After rigorous screening for candidate biomarkers and validation with a targeted metabolomic approach, three metabolites, nomilin, Lys-Leu, and hawkinsin, emerged as significantly elevated biomarkers in H3K27M-mutant BSG urine samples. The biomarker panel combining the three metabolites had a diagnostic area under the curve (AUC) of approximately 75%. Furthermore, the biomarker panel improved the prediction accuracy of radiomics/clinical models to an AUC value high as 93.38%.

Conclusions
A urinary metabolite biomarker panel that exhibited high accuracy for non-invasive prediction of the H3K27M mutation status in BSG patients was identified. This panel has the potential to improve the predictive performance of current radiomics models or clinical features.
Phenylalanine metabolism-dependent lignification confers rhizobacterium-induced plant resistance
Authors: Li Qi , Liu Zhuangzhuang , Jiang Zexuan , Jia Mingyun , Hou Zhaoqi , Dou Daolong , Yu Jinping 
Published: February 2025

Abstract
Phenylalanine metabolism serves as an important route for the production of diverse secondary metabolites including phenylpropanoids. The phenylpropanoid pathway is involved in plant immunity, but whether it can regulate rhizobacteria-induced resistance is poorly understood. In this study, we confirmed a growth-promoting rhizobacterium strain JR48 could induce resistance, strengthen salicylic acid (SA) signaling, and increase lignin content during Phytophthora capsici infection. We conducted transcriptome sequencing to analyze the effect of JR48 on the expression of pepper (Capsicum annuum L.) genes, generated transgenes and loss-of-function genetic materials to specify the function of peroxidase genes, and implemented metabolomics analysis to uncover the resistance-inducing metabolites of JR48. JR48 activated expression of several pepper peroxidase genes in the phenylpropanoid pathway during pathogen infection. These peroxidases positively regulated lignification-mediated pathogen resistance, and the phenylpropanoid pathway acted downstream of SA signaling to confer JR48-induced resistance. Further, JR48 was capable of producing phenylpyruvate to enhance phenylalanine accumulation, thereby reinforcing phenylalanine metabolism-dependent lignification and resistance. Our results revealed that JR48 produces phenylpyruvate to refuel phenylalanine metabolism and reinforces SA signaling to further activate expression of peroxidase genes. This study uncovers immune components previously hidden in metabolic pathways and a recent mechanism underlying rhizobacteria-induced plant resistance.
Giant cell arteritis mimics with severe consequences: a long-term monocentric inception cohort
Authors: Parreau Simon , Cayrou Cory , Dumonteil Stéphanie , Laburthe Sébastien , Bosphore Gregory , Desvaux Edouard , Ratti Nina , Lopez Jean-Guillaume , Margotonne Menfild , Couillard Florence , Bouquet Remy , Salvador Bastien , Palat Sylvain , Foré Romain , Gondran Guillaume , Bezanahary Holy , Fauchais Anne-Laure , Liozon Eric , Ly Kim-Heang 
Published: February 2025

Abstract

Objectives
To describe patients who underwent a temporal artery biopsy (TAB) for suspected GCA but were given a different diagnosis. We focused on a subset of alternate diagnoses mimicking GCA with ominous consequences of a delayed diagnosis or undue glucocorticoid treatment.

Methods
This was a single-centre retrospective study. All patients (n = 579) underwent a TAB for initially suspected GCA and were recruited from 2005 to 2023. Four groups were defined: GCA with a positive TAB (n = 248); GCA with a negative TAB (n = 135); rapid alternative diagnoses without ominous consequences (usual mimics, n = 177); and alternative diagnoses with severe consequences (ominous mimics, n = 19).

Results
Of the 19 ominous mimics (10% of all mimics), 9 had major diagnostic delays leading to severe outcomes and 12 patients suffered severe side effects from glucocorticoid treatment. The ominous mimics had higher ACR/EULAR 2022 scores than the usual mimics (6.9 vs 4.5), but they had scores similar to those with GCA and a negative TAB. The mean time to an alternative diagnosis was 66 days for the ominous mimics, and the average diagnostic delay of 145 days was much longer than that in the other groups, with a high mortality rate of 68%.

Conclusion
Misdiagnosing GCA has severe consequences in a few patients. Classification criteria often fail to differentiate mimics from true GCA. Clinician vigilance, histology proof and imaging tools are critical for ruling out GCA and should be used more widely. Reducing diagnostic delay is essential for improving patient survival in severe mimics cases.
Cut-off matters in the interpretation of myositis antibodies by line immunoassay
Authors: Wei Xiumei , Yun James , He Jianna , Sturgess Allan 
Published: February 2025

Abstract

Objectives
To evaluate the performance of a commercial line immunoassay (LIA) in cohorts of healthy controls (HC), disease controls (DC), and patients with idiopathic inflammatory myopathies (IIMs), and investigate whether different cut-offs would enhance the accuracy of myositis antibodies (MAs) by LIA.

Methods
Sera from patients with positive MAs (n = 118), DC (n = 124) and HC (n = 60), were analysed for MAs using EUROLINE Myopathies 16 Ag LIA (EUROIMMUN).

Results
The newly established MAs cut-offs resulted in significantly lower both false-positive and multiple positive rates compared with the manufacturer’s single cut-off, from 36.7% to 5.0% and 7.2% to 1.1% in controls, and 45.8% to 23.8% and 23.7% to 15.5% in patients with positive MAs cohorts, respectively. Furthermore, the positive predictive value (PPV) of MAs for IIMs or interstitial lung disease (ILD) increased significantly from 47.5% to 66.7%.

Conclusion
Establishment of local cut-offs and cross-reference ANA findings can significantly enhance the assay’s performance and increase the confidence in interpreting MAs results by LIA. It is important to be aware of the low PPV for most MAs in real-world cohorts, thus, the investigation of MAs should be approached as confirmatory or differential diagnosis rather than a screening tool in IIMs.
Urological cancer risk in patients with rheumatoid arthritis compared to matched controls: A nationwide cohort study
Authors: Lee Dagyeong , Jeon Keun Hye , Jung Jinhyoung , Han Kyungdo , Cho Mi Hee , Cho In Young , Shin Dong Wook 
Published: February 2025

Abstract

Objective
Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with several comorbidities, including an increased risk of certain cancers. This study aimed to investigate the potential associations between RA and increased risk of urological cancers—specifically kidney, bladder, prostate and testicular cancers—and the influence of RA serological status on this risk.

Methods
This retrospective cohort study used data from the Korean National Health Insurance System database (2010–2020), including patients with RA and a 1:5 matched non-RA population. RA patients were grouped according to serological status. The primary outcome was newly diagnosed urological cancer, and its association with RA was analyzed by Cox proportional hazards regression analyses adjusting for potential confounders.

Results
RA patients had an increased risk of kidney cancer compared with the non-RA population (adjusted hazard ratio [aHR], 1.34 [95% confidence interval (CI), 1.04–1.78]). The risk of kidney cancer was even higher in women with RA (aHR 1.57 [95% CI: 1.10, 2.24]). However, the risk of bladder, prostate and testicular cancers was not associated with RA (bladder cancer, aHR 1.24, 95% CI 0.95–1.62; prostate cancer, aHR 1.13, 95% CI 0.94–1.35; testicular cancer, aHR 2.31, 95% CI 0.44–12.20). No significant difference in urological cancer risk was found according to serological status.

Conclusions
RA patients have a higher risk of kidney cancer than the general population. Further research is needed to understand the mechanisms underlying the association between RA and kidney cancer to optimize cancer prevention and screening strategies.
Evaluation of increasing levels of mycotoxin-containing corn fines and mitigants on nursery pig growth performance
Authors: Paczosa D B , Chevalier T B , Adedokun S A , Zheng L , Lindemann M D 
Published: February 2025

Abstract
The effects of feeding corn fines (screenings) containing mycotoxin levels greater than the FDA guidance (fumonisins) and advisory (deoxynivalenol) levels were evaluated using 150 crossbred pigs (initial BW: 6.42 ± 0.06 kg; 90 barrows and 60 gilts) in an 8-week study by adding contaminated corn fines to create six diets. The corn fines used contained prestudy analyzed mycotoxin levels of 20,334 ppb total fumonisin, 1,499 ppb zearalenone, and 5,075 ppb total deoxynivalenol. The corn fines were added into a corn-soybean meal basal diet at 0, 20, 40, and 60% corn fines (Diets 1-4, respectively). Diet 5 was created by adding 40 ppm of boron (as sodium tetraborate decahydrate, 11.34% B) to Diet 4. Diet 6 was created by adding 0.25% Biofix Plus with FUMzyme (BPF; dsm-firmenich, Plainsboro, NJ) to Diet 4. Dietary treatments were fed for 6 weeks; after that, all pigs received a common corn-soybean meal basal diet without fines for about 2 weeks. The lightest, median, and heaviest pigs in a pen were selected at Wk 3, and serum was collected from those pigs on Wk 3, 6, and 8. Serum clinical chemistry and sphinganine:sphingosine ratio (SA:SO) were determined at Wk 6. Increasing fines linearly decreased ADG during Wk 1-6 (P = 0.03). Comparing Diets 4 and 5 to Diet 1 during Wk 1-6, there was a decrease in ADG (P &lt; 0.05); subsequently, the difference in Diets 4 and 5 compared to Diet 1 was no longer significant for Wk 1-8. Comparing Diet 6 to Diets 1 and 4 during Wk 1-6, pigs fed Diet 6 were able to recover 57% of the lost ADG that occurred when corn fines were increased from 0 to 60%. During Wk 7-8 (all pigs on a common diet), pigs on Diets 5 and 6 had an increase in ADG compared to Diet 1. SA:SO linearly increased as fines in the diet increased (Diets 1-4; P = 0.001), but the addition of BPF ameliorated 95% of this increase. In conclusion, as mycotoxins increased, pigs exhibited negative effects in ADG, but the additive Biofix Plus with FUMzyme ameliorated a portion of these effects. Further, the recovery from Wk 7-8 from all pigs does show the importance of feeding clean corn to optimize ADG, ADFI, and gain/feed ratio.
Trends in Operative Timing for Acute Traumatic Central Cord Syndrome
Authors: Gagliardi Thomas A. , Fleisher Ilan , Lapow Justin , Spirollari Eris , Sullivan Timothy , Carr Alexis , Berardino Kevin , Kinon Merritt , Patel Harshadkumar 
Published: February 2025

Study Design:
Retrospective cohort study.

Objective:
To analyze national trends in the management of acute traumatic central cord syndrome.

Summary of Background Data:
Acute traumatic central cord syndrome (ATCCS) is the most common incomplete spinal cord injury. Initial management involves decompression and stabilization of the cervical spinal cord. On the basis of mixed literature regarding operative timing for ATCCS, we aimed to evaluate trends in early, late, and delayed surgery over the last 5–10 years and compare their respective outcomes.

Methods:
Data were obtained from the National Inpatient Sample (NIS) using specific ICD-10 codes. Baseline demographics, comorbidities, and outcomes were evaluated. These patients were grouped based on whether central cord syndrome (CCS) operative treatment was early (within 24h of admission), late (between 24 and 48h of admission), or delayed (after 48h of admission).

Results:
A total of 21,265 patients underwent operative management for ATCCS; 16.7% received early operative management, 35.6% received late operative management, and 47.6% received delayed operative management. Compared with the total cohort, the delayed operative management group was more likely to contain patients with obesity (7.1% vs. 6.3%, P<0.001), chronic obstructive pulmonary disease (COPD) (12.9% vs. 11.1%, P<0.001), and diabetes mellitus (28.1% vs. 26.1%, P<0.001). Early operative management was more likely in patients with plegia (24.7% vs. 17%, P<0.001) and bowel/bladder dysfunction (14.6% vs. 9.5%, P<0.001) and was independently associated with lower rates of prolonged length of stay (LOS) (OR=0.71) and acute kidney injury (AKI) (OR=0.696).

Conclusions:
Our analysis of the trends in operative timing for ATCCS demonstrated an overall increase in the rate of early operative management and a decrease in the rate of delayed operative management. These findings mirror the current evolution of the literature on the topic. Nuances in early versus late outcomes should be used to help decision making related to operative timing in ATCCS.

Level of Evidence:
Level III.
Technical Refinements of Supraclavicular Artery Island Flap With Submuscular Tunnel for Reconstruction of Remote Head and Neck Postburn Scars
Authors: Ellabban Mohamed A. , Steinvall Ingrid , Sjöberg Folke , Elmasry Moustafa 
Published: February 2025

Background:
The supraclavicular artery island flap (SCAIF) has been used extensively to reconstruct postburn scars in the head and neck region. Its landmark and vascular supply from the supraclavicular artery have been demonstrated before. The aim was to assess its versatility following an increase in pedicle length to be supplied by the transverse cervical artery, along with tunneling the pedicle under the sternocleidomastoid muscle to reach distant sites that the classic SCAIF could not reach.

Methods:
A retrospective analysis was conducted of 25 consecutive patients in whom SCAIFs were performed to reconstruct remote head and neck postburn scars. Pedicle length, flap diameter, and complications were recorded with demographic and burn-related data.

Results:
The study included 18 (72%) men and 7 (18%) women. The mean age was 15.7 years, and the mean injury time was 15 months before flap transfer. Isolated neck injury was the most affected site (44%). The mean length and width of the SCAIF were 16.6 and 6.5 cm, respectively. The mean length of its extended vascular pedicle based on transverse cervical artery was 7.2 cm. The donor site was closed primarily in all cases. All flaps survived completely, except 2 (8%) that exhibited partial necrosis.

Conclusions:
The SCAIF is reliable for reconstructing postburn deformities in the head and neck region. Our results indicate that the increased pedicle length and the submuscular tunnel allow reliable distant flap transfer without the risk of excessive traction or vessel kinking.
Proposed Probabilistic Optimization of Radioactive Waste Disposal Facility Design Considering Long-term Uncertainty
Authors: Kuroda Kazuma , Nakabayashi Ryo , Sugiyama Daisuke 
Published: February 2025

Abstract
In the optimization of radioactive waste disposal facility design, it is important to compare multiple facility design options with the aim of reducing the effective dose as low as reasonably achievable. In this study, a methodology for optimizing the facility design using a probabilistic approach was proposed, and two case studies were provided the application of the methodology and interpretation of the dose distributions. This methodology incorporates the time integration of the 95th percentile value and the sum of coefficients of variation extracted from the probability distribution of dose profile over time as the indicators for relative comparison on the optimization. This methodology enables consideration of the dose with uncertainty for the entire long-term assessment period in the optimization. This allows a more multifaceted comparison of options and is expected to improve the ability to explain optimization with the consideration of long-term uncertainty. While various factors including economic, social, and possibly others are relevant to the decision process, this study focuses on the dose estimations as an indicator for optimization. In the case studies, intermediate-depth disposal in Japan, which is one of the disposal systems of low-level radioactive waste, is used as an example and the groundwater release scenario was the focus. The comparison of multiple options in low-diffusivity and low-permeability layers were assumed. These are the important factors in the migration of radioactive nuclides, while other parameters can also be considered in optimization by using the proposed methodology.