bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine Learning-Assisted High-Content Imaging Analysis of 3D MCF7 Microtissues for Estrogenic Effect Prediction
Authors: Li Hui , Seada Haitham , Madnick Samantha , Zhao He , Chen Zhaozeng , Li Fengcheng , Zhu Feng , Hall Susan , Boekelheide Kim 
Published: October 2023

Abstract
Endocrine-disrupting chemicals (EDCs) pose a significant threat to human well-being and the ecosystem. However, in managing the many thousands of uncharacterized chemical entities, the high-throughput screening of EDCs using relevant biological endpoints remains challenging. Three-dimensional (3D) culture technology enables the development of more physiologically relevant systems in more realistic biochemical microenvironments. The high-content and quantitative imaging techniques enable quantifying endpoints associated with cell morphology, cell-cell interaction, and microtissue organization. In the present study, 3D microtissues formed by MCF-7 breast cancer cells were exposed to the model EDCs estradiol (E2) and propyl pyrazole triol (PPT). A 3D imaging and image analysis pipeline was established to extract quantitative image features from estrogen-exposed microtissues. Moreover, a machine-learning classification model was built using estrogenic-associated differential imaging features. Based on 140 common differential image features found between the E2 and PPT group, the classification model predicted E2 and PPT exposure with AUC-ROC at 0.9528 and 0.9513, respectively. Deep learning-assisted analysis software was developed to characterize microtissue gland lumen formation. The fully automated tool can accurately characterize the number of identified lumens and the total luminal volume of each microtissue. Overall, the current study established an integrated approach by combining non-supervised image feature profiling and supervised luminal volume characterization, which reflected the complexity of functional ER signaling and highlighted a promising conceptual framework for estrogenic EDC risk assessment.
Patients suffering traumatic brain injury: characteristics, primary referral and mortality – A population-based follow-up study
Authors: Seidenfaden Sophie-Charlott , Pedersen Claus Kjær , Juul Niels , Kirkegaard Hans , Bøtker Morten Thingemann 
Published: October 2023

Abstract
Background
Traumatic brain injury is a potential high-risk condition. Appropriate care pathways, including prehospital triage and primary referral to a specialized neurosurgical center, improves neurological outcome and survival. The aim of this study was to examine TBI patient and injury characteristics, the way of entering into the health care system, place of primary referral and the associated 30-day and 1-year mortality rates in TBI patients with confirmed intracranial lesions.
Methods
This was a retrospective observational population-based follow-up study conducted in Central Denmark Region from 1 February 2017 to 31 January 2019. We included all hospital contacts of patients ascribed a predefined TBI ICD-10 diagnosis code in the Danish National Patient Register. The obtained TBI cohort was merged with prehospital data from the Prehospital Emergency Medical Services, Central Denmark Region, and vital status from the Danish Civil Registration System. Binary logistic regression analysis of mortality was applied.
Results
A total of 5,257 first TBI hospital contacts were included in the cohort. Of these, 1,430 (27.2%) entered the health care system by 112-call. TBI patients triaged by 112-call were more likely to receive the highest level of emergency response, second-tier resources and were more frequently referred directly to a specialized center than patients entering through general practioner or other health care personnel. In the subgroup of 1188/5257 (22.4%) patients with confirmed intracranial lesions, we found no difference in risk ratio of 30-day (RR 1.04 (95%CI 0.65 − 1.63)) or 1-year (RR 0.96 (95%CI 0.72–1.25)) all-cause mortality between patients primarily referred to a regional hospital or specialized center when adjusting for age, sex, comorbidities, antiplatelet/-coagulant treatment and type of intracranial lesions.
Conclusion
TBI patients mainly enter the health system by contact to general practitioner or other health care professionals, but patients entering through 112-call are more frequently triaged directly to specialized center. We were unable to demonstrate any significant difference in adjusted 30-day and 1-year mortality according to primary referral to a specialized center or not.
DNA polymerase beta connects tumorigenicity with the circadian clock in liver cancer through the epigenetic demethylation of Per1
Authors: Liu Chang , Chen Siyu , Zhang Wenxiang , Li Xiao 
Published: October 2023

Abstract
The circadian-controlled DNA repair exhibits a strong diurnal rhythm. Disruption in circadian clock and DNA repair is closely linked with hepatocellular carcinoma (HCC) progression, but the mechanism remains unknown. Here, we show that polymerase beta (Polb), a critical enzyme in the DNA base excision repair pathway, is rhythmically expressed at the translational level in mouse livers. Hepatic Polb dysfunction dampens clock homeostasis, whereas retards HCC progression, through methylation of the 4th CpG island on the 5'UTR of clock gene Per1. Clinically, POLB is overexpressed in human PolbHCC samples and positively associated with poor prognosis. Furthermore, the hepatic rhythmicity of Polb protein expression is orchestrated by Calreticulin (Calr). Our findings provide important insights into the molecular mechanism underlying the synergy between clock and food signals on the Polb-driven BER system and reveal new clock-dependent carcinogenetic effects of Polb. Therefore, chronobiological modulation of Polb may help to promote precise interventions for HCC.
Gravitational form factors of the proton from near-threshold vector meson photoproduction
Authors: Wang Xiao-Yun 
Published: October 2023

Abstract
We embark on a systematical analysis of the quark and gluon gravitational form factors (GFFs) of the proton, by connecting energy-momentum tensor and the near-threshold vector meson photoproduction (NTVMP). Concretely, the quark contributions of GFFs are determined unprecedentedly by global fitting the cross section of the lightest vector meson ρ0 photoproduction. Combined with the gluon GFFs achieved from heavy quarkonium J/ψ photoproduction data, the complete GFFs are obtained and compared with the deeply virtual Compton scattering experimental results and LQCD determinations. The profound implications of this finding cannot be overstated, as it opens new avenues for obtaining comprehensive information on GFFs. Naturally, this work is not only an important basis for delving the proton enigmatic properties, but also have significance theoretical guiding for future JLab and EICs experimental measurements.
DAIR in treating late-phase infection after total knee arthroplasty using continuous local antibiotic perfusion therapy: A case series study
Authors: Zenke Yukichi , Ando Kohei , Motojima Yasushi , Kosugi Kenji , Hamada Daishi , Okada Yasuaki , Sato Naohito , Shinohara Daichi , Suzuki Hitoshi , Kawasaki Makoto , Sakai Akinori 
Published: October 2023

Abstract
Background: Antimicrobial agents are administered via intramedullary antibiotic perfusion (iMAP)/intrasoft tissue antibiotic perfusion (iSAP) to infected lesions to control osteoarticular and soft tissue infections. Continuous local antibiotic perfusion (CLAP) has been reported to be useful. This study aimed to investigate the outcomes of DAIR combined with CLAP for delayed infection after total knee arthroplasty performed at our hospital.
Subjects and methods: Six patients (male; one case, female; five cases, mean age 79.5 years (70-94)) underwent CLAP for delayed infection after TKA at our hospital between July 2020 and June 2022. They were followable for at least one year after surgery. Seven months (17-219), with a mean follow-up of 24.3 months (12-36). In addition to direct debridement and insert exchange, systemic antimicrobial treatment and CLAP with gentamicin were performed. We investigated the organisms causing the inflammation, the duration of iMAP/iSAP implantation, the maximum daily dose of GM, the maximum GM blood concentration, and the presence or absence of GM-induced adverse events.
Result: Two of six patients had a recurrence of infection at five weeks and five months after initial CLAP and required repeat CLAP treatment, but all patients were able to preserve their components. The organisms responsible for the flare-ups were MSSA in three cases; ESBL-producing E. coli, mixed MSSA and streptococcal infection, and Klebsiella pneumonia in one case each; and unknown pathogens in one case. CLAP therapy for all patients was administered eight times in 6 cases: iMAP, mean: 10.0 days (5-16); iSAP, mean: 19.3 days (15-28); GM dose, mean: 162.5 mg/day (80-240); and GM blood concentration, mean: 1.4 µg/mL (0.2-5.0). Adverse events included one case of reversible acute kidney injury during CLAP in a patient with recurrent infection.
Summary: DAIR with CLAP for delayed post-TKA infection can be a useful treatment option to preserve components and allow the infection to subside, provided the implant is not markedly loosened.
Comparative physiological and transcriptome analysis revealed the role of cerium in alleviating copper stress in Dendrobium nobile Lindl.
Authors: Li Xuebing , Ma Jie , Fan Yijun , Xu Erya , Xu Linlong , Liu Yuanyuan , Wu Junlan , Liu Haolin , Wang Hui , Li Ting , He Siyu , Luo Ao 
Published: October 2023

Abstract
Low concentrations of rare earth elements can be used as mitigants to alleviate metal toxicity in plants. The aim of this experiment was to investigate the mechanism of cerium (Ce) mitigation of copper (Cu) stress in Dendrobium nobile Lindl. It was found that Cu treatment caused significant stress, while Ce spray significantly improved the growth under Cu stress and reduced the Cu content in the plant by 9.48%. Ce promoted photosynthesis of D. nobile and enhanced the ability to scavenge reactive oxygen species by increasing the activity of antioxidant enzymes. Ce combines with heavy metal ions to form chelates and transports Cu into the vesicles, thus reducing the toxicity of metals to plants. Transcriptome analysis revealed 959 differential genes in the Cu + Ce group compared to the Cu group (511up, 458down). Analysis of differential genes related to metabolic pathways for detoxification revealed that Ce can enhance tolerance of D. nobile under Cu stress through various pathways such as regulated metabolic pathways Isoquinoline alkaloid biosynthesis, MAPK signaling pathway, Phenylpropanoid Bioynthesis, Plant hormone signal transduction, Pyruvate metabolism pathway and ABC transporter to regulate GSH, amino acids, metallothionein, thus affecting antioxidant enzyme activity, synergistic ion transport and metal chelate synthesis. GST, AOC3, cat, PP2C, OMT, GCSH, N4OMT, ACS, MKK9, CML may be the key genes in D. nobile to resist Cu stress. This study initially reveals the mechanism of Ce alleviation of Cu stress and lays a theoretical foundation for further research on the molecular regulatory mechanism of D. nobile in adversity.
Periostin+ macrophages improved long bone regeneration in a mechanosensitive manner
Authors: Liu Chao , Wang Ziyan , Lin Minmin , Pan Yonghao , Liu Yang , Yang Chengyu , Wu Jianqun , Wang Yan , Yan Bingtong , Zhou Jingjing 
Published: October 2023

Abstract
Macrophages are pivotal in the inflammatory and remodeling phases of fracture repair. Here, we investigate the effect of periostin expressed by macrophages on bone regeneration in a monocortical tibial defect (MTD) model. In this study, we show that periostin is expressed by periosteal macrophages, primarily the M2 subtype during bone regeneration. The deletion of periostin in macrophages reduces cortical bone thickness, disrupts trabecular bone connectivity, exacerbates repair impairment, and hinders M2 macrophage polarization. Mechanical stimulation has been shown to be as a regulator of periostin in macrophages. By activating transforming growth factor-β (TGF-β) and phosphorylating Smad2/3, it increases periostin expression in macrophages and induces M2 polarization. This mechanosensitive effect also reverses the delayed bone repair induced by periostin deficiency in macrophages by strengthening the angiogenesis-osteogenesis coupling. In addition, transplantation of mechanically-conditioned macrophages into the periosteum over a bone defect results in substantially enhanced repair, confirming the critical role of macrophage-secreted periostin in bone repair. In summary, our results suggest one mechanism of mechanically stimulated bone formation is the regulation of periostin expression and M2 subtype polarization in macrophages via the TGF-β/Smad2/3 signaling pathway, and demonstrates mechanically-conditioned macrophages as a promising therapeutic strategy for enhancing bone repair.
Sex dimorphism in behavioral, seizure, and pain threshold in allergic rhinitis model; the role of DNMT1 in neuroinflammation
Authors: Elahi Mohammad , Soltani Zahra Ebrahim , Afrooghe Arya , Ahmadi Elham , Dehpour Ahmad Reza 
Published: October 2023

Abstract
Our previous research demonstrated that allergic rhinitis could impact behavior and seizure threshold in male mice. However, due to the complex hormonal cycles and hormonal influences on behavior in female mice, male mice are more commonly used for behavioral tests. In this study, we aimed to determine whether these findings were replicable in female mice and to explore the potential involvement of sexual hormones in regulating neuroinflammation in an allergic model.
Our results indicate that pain threshold was decreased in female mice with allergic rhinitis and the levels of IL-23/IL-17A/IL-17R were increased in their Dorsal root ganglia. However, unlike males, female mice with AR did not display neuropsychological symptoms such as learning and memory deficits, depression, and anxiety-like behavior. This was along with decreased levels of DNA methyl transferase 1 (DNMT1) and inflammatory cytokines in their hippocampus. Ovariectomized mice were used to mitigate hormonal effects, and the results showed that they had behavioral changes and neuroinflammation in their hippocampus similar to male mice, as well as increased levels of DNMT1.
These findings demonstrate sex differences in how allergic rhinitis affects behavior, pain sensitivity, and seizure thresholds. Furthermore, our data suggest that DNMT1 may be influenced by sexual hormones, which could play a role in modulating inflammation in allergic conditions.
Impact of intrapartum oxytocin administration on neonatal sucking behavior and breastfeeding
Authors: Omaru Machiko , Kajiwara Setsu , Wakamatsu Eri , Kuroishi Sumiko , Ochiai Yukifumi , Oniki Kentaro , Morokuma Seiichi 
Published: October 2023

Abstract
This study aimed to examine the effect of intrapartum oxytocin administration on neonatal sucking behavior and breastfeeding. A total of 64 pairs (29 in the group treated with intrapartum oxytocin and 35 in the control group) of normal infants within 24–48 h of birth and their mothers were recruited. Sucking ability was evaluated by measuring Non-Nutritive Sucking (NNS) for 5 min. Data on the rate of exclusive breastfeeding at 1 month postpartum were collected. In the adjusted multiple regression models, intrapartum oxytocin exposure was significantly associated with fewer total NNS bursts (95% confidence interval (CI), -6.811 to -0.311), longer pause times (95% CI, 0.320 to 9.223), and greater pause-time variability (95% CI, 4.453 to 62.738). Effects estimated using structural equation modeling revealed that intrapartum oxytocin exposure had a significant negative and direct effect on the practice of exclusive breastfeeding 1 month postpartum (β=-.238, p = 0.047). However, no NNS-mediated indirect effects were observed. This report demonstrates that infants born to mothers who receive intrapartum oxytocin may have impaired sucking ability for at least the first 48 h after birth, and breastfeeding support should be provided.
A Comparison of Embedding Aggregation Strategies in Drug-Target Interaction Prediction
Authors: Iliadis Dimitrios , De Baets Bernard , Pahikkala Tapio , Waegeman Willem 
Published: October 2023

Abstract
The prediction of interactions between novel drugs and biological targets is a vital step in the early stage of the drug discovery pipeline. Many deep learning approaches have been proposed over the last decade, with a substantial fraction of them sharing the same underlying two-branch architecture. Their distinction is limited to the use of different types of feature representations and branches (multi-layer perceptrons, convolutional neural networks, graph neural networks and transformers). In contrast, the strategy used to combine the outputs (embeddings) of the branches has remained mostly the same. The same general architecture has also been used extensively in the area of recommender systems, where the choice of an aggregation strategy is still an open question. In this work, we investigate the effectiveness of three different embedding aggregation strategies in the area of drug-target interaction (DTI) prediction. We formally define these strategies and prove their universal approximator capabilities. We then present experiments that compare the different strategies on benchmark datasets from the area of DTI prediction, showcasing conditions under which specific strategies could be the obvious choice.
Comparison between microphone and accelerometer signals for chatter identification in milling processes
Authors: Couto Alison de Andrade , Almeida Ubiratã , Pereira Igor , Guimarães Gustavo 
Published: October 2023

Abstract
Machining operations may lead to chatter, a harmful phenomenon to the process that has to be avoided. The chatter identification is an important method to understand the machining process through the vibrations signals and avoid the conditions where chatter is more likely to be present. In this work, two approaches for milling chatter identification were studied, the first one using the signal by a microphone sensor and the second one using accelerometers in two different points, with the objective of making a comparison of which is the most suitable for a case with a long tool and low axial depth of cut. Frequency and time domain analyzes were performed, the results for both cases show the chatter in a specific cutting condition, however, the regenerative phenomenon was more evidently identified through the microphone. The obtained results will also be used in a practical context for the validation of a Stability Lobe Diagrams under development.
Hydrogen production with reduced energy consumption for use in fuel cells and energy sector
Authors: Nefedov Volodymyr , Polishchuk Yuliya , Matveev Vadim , Sukhyi Mykhailo 
Published: October 2023

Abstract
The possibility of increasing the hydrogen release rate and reducing energy consumption was analyzed using a system in which the anodic process of metal (aluminum) dissolution occurred on one electrode and the process of H2 release - on the other (nickel) electrode. The possibility of generating hydrogen with a current density of ~ 400 mA cm–2 in NaOH solutions with a concentration of 6 ÷ 8 mol L–1 at a cell voltage of ~ 0.5 V was confirmed. When the electrodes were short-circuited, hydrogen was generated on nickel when aluminum was dissolved at a rate corresponding to current density ~ 100 mA cm–2. The possibility of simultaneous hydrogen production and electricity generation in the system under consideration was shown. It was found that the maximum net power was generated in 6 M NaOH. The specific power in such a solution can reach a value of 8 W cm–2 at a cell voltage of about 0.15 V. In this case, the hydrogen release rate corresponded to a current density of 60 mA cm–2.
Methacrylated poly(glycerol sebacate) as a photocurable, biocompatible, and biodegradable polymer with tunable degradation and drug release kinetics
Authors: Bice Mei-Li L. , Ortega Valentina L. , Yu Marina H. , McHugh Kevin J. 
Published: October 2023

Abstract
Poly(glycerol sebacate) (PGS) is a biodegradable, elastomeric polymer that has been explored for applications ranging from tissue engineering to drug delivery and wound repair. Despite its promise, its biomedical utility is limited by its rapid, and largely fixed, degradation rate. Additionally, its preparation requires high temperatures for long periods of time, rendering it incompatible with heat-sensitive molecules, complex device geometries, and high-throughput production. In this study, we synthesized methacrylated PGS (PGS-M), imparting the ability to rapidly photocross-link the polymer. Increasing the degree of methacrylation was found to slow PGS-M degradation; PGS-M (5.5 kDa) disks with 21% methacrylation lost 43% of their mass over 11 weeks in vivo whereas 47% methacrylated disks lost just 14% of their mass over the same period. Increasing the methacrylation also extended the release of encapsulated daunorubicin by up to two orders of magnitude in vitro, releasing drug over months instead of one week. Like PGS, PGS-M exhibited good biocompatibility, eliciting limited inflammation and fibrous encapsulation when implanted subcutaneously. These studies are the first to perform long-term studies demonstrating the ability to tune PGS-M degradation rate, use PGS-M to release drug, demonstrate sustained release of drug from PGS-M, and evaluate PGS-M behavior in vivo. Taken together, these studies show that PGS-M offers several key advantages over PGS for drug delivery and tissue engineering, including rapid curing, facile loading of drugs without exposure to heat, tunable degradation rates, and tunable release kinetics, all while retaining the favorable biocompatibility of PGS.
Development and internal validation of a nomogram for sleep quality among Chinese medical student
Authors: Lv Zhen , Jun Chen , Yang Handong , Chen Jishun , Li Dongfeng , Xu Hao , Wang Ying , Guo Huailan , Zhang Ningrui , Liu Zhixin , Min Xinwen , Wu Wenwen 
Published: October 2023

Abstract
Objective
Poor sleep quality is common among Chinese medical students. Therefore, identifying predictors is necessary to implement individualized interventions. This study aimed to develop and validate a nomogram to predict poor sleep quality among Chinese medical students.
Methods
A cross-sectional study was used to collect data among Chinese medical students at the Hubei University of Medicine. A total of 2038 medical students were randomly divided into training (70%) and validation (30%) groups. Multivariable logistic regression analysis was performed to examine factors associated with sleep quality. Thereafter, these factors were used to develop a nomogram for predicting sleep quality. The predictive performance was evaluated by receiver operating characteristics curve (ROC) analysis, calibration curve analysis, and decision curve analysis (DCA).
Results
A total of 70.4% of medical students in the study reported poor sleep quality. The predictors of sleep quality included grade, gender, self-assessment of interpersonal relationships, and self-assessment of health status. The scores of the nomogram ranged from 28 to 176, and the corresponding risk ranged from 0.50 to 0.95. The calibration curve showed that the nomogram had good classification performance. The area under the curve (AUC) of the ROC for the training group is 0.676, and that for the validation group is 0.702. The DCA demonstrated that the model also had good net benefits.
Conclusions
The nomogram prediction model has sufficient accuracies, good predictive capabilities, and good net benefits. The model can also provide a reference for predicting the sleep quality of medical students.