bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ibrutinib disrupts blood-tumor barrier integrity and prolongs survival in rodent glioma model
Authors: Lim Sanghee , Kwak Minhye , Kang Jeonghan , Cesaire Melissa , Tang Kayen , Robey Robert W. , Frye William J. E. , Karim Baktiar , Butcher Donna , Lizak Martin J. , Dalmage Mahalia , Foster Brandon , Nuechterlein Nicholas , Eberhart Charles , Cimino Patrick J. , Gottesman Michael M. , Jackson Sadhana 
Published: April 2024

Abstract
In malignant glioma, cytotoxic drugs are often inhibited from accessing the tumor site due to the blood-tumor barrier (BTB). Ibrutinib, FDA-approved lymphoma agent, inhibits Bruton tyrosine kinase (BTK) and has previously been shown to independently impair aortic endothelial adhesion and increase rodent glioma model survival in combination with cytotoxic therapy. Yet additional research is required to understand ibrutinib’s effect on BTB function. In this study, we detail baseline BTK expression in glioma cells and its surrounding vasculature, then measure endothelial junctional expression/function changes with varied ibrutinib doses in vitro. Rat glioma cells and rodent glioma models were treated with ibrutinib alone (1–10 µM and 25 mg/kg) and in combination with doxil (10–100 µM and 3 mg/kg) to assess additive effects on viability, drug concentrations, tumor volume, endothelial junctional expression and survival. We found that ibrutinib, in a dose-dependent manner, decreased brain endothelial cell–cell adhesion over 24 h, without affecting endothelial cell viability (p < 0.005). Expression of tight junction gene and protein expression was decreased maximally 4 h after administration, along with inhibition of efflux transporter, ABCB1, activity. We demonstrated an additive effect of ibrutinib with doxil on rat glioma cells, as seen by a significant reduction in cell viability (p < 0.001) and increased CNS doxil concentration in the brain (56 ng/mL doxil alone vs. 74.6 ng/mL combination, p < 0.05). Finally, Ibrutinib, combined with doxil, prolonged median survival in rodent glioma models (27 vs. 16 days, p < 0.0001) with brain imaging showing a − 53% versus − 75% volume change with doxil alone versus combination therapy (p < 0.05). These findings indicate ibrutinib’s ability to increase brain endothelial permeability via junctional disruption and efflux inhibition, to increase BTB drug entry and prolong rodent glioma model survival. Our results motivate the need to identify other BTB modifiers, all with the intent of improving survival and reducing systemic toxicities.
Digital setup accuracy for moderate crowding correction with fixed orthodontic appliances: a prospective study
Authors: Kusaibati Abdalrahman Mohieddin , Sultan Kinda , Hajeer Mohammad Younis , Gkantidis Nikolaos 
Published: April 2024

Abstract
Objectives
To evaluate the accuracy of a semi-automatic 3D digital setup process in predicting the orthodontic treatment outcome achieved by labial fixed appliances.

Subjects and Methods
Twenty-five adult patients (18 to 24 years old) with class I malocclusion and moderate crowding were prospectively enrolled and received treatment on both jaws through the straight-wire technique. Prior to treatment commencement, a semi-automatic digital setup simulating the predicted treatment outcome was performed for each patient through Orthoanalyzer software (3Shape®, Copenhagen, Denmark) to obtain the prediction model. This was compared to the final outcome model through 3D superimposition methods. Metric variables and inspection of color-coded distance maps were used to detect how accurately the digital setup predicts the actual treatment outcome.

Results
The mean absolute distances (MAD) between the superimposed dental arches of the predicted and the final models were: 0.77 ± 0.13 mm following superimposition on the palate, 0.52 ± 0.06 mm following superimposition on the maxillary dental arch, and 0.55 ± 0.15 mm following superimposition on the mandibular dental arch. The MAD at the palatal reference area was 0.09 ± 0.04 mm. Visualization of color-coded distance maps indicated that the digital setup accurately predicted the final teeth position in a few cases. Almost half of the cases had posteriorly wider upper and lower dental arches and palatally/lingually positioned or inclined anterior teeth, whereas the rest still showed errors within 2–3 mm, distributed over the entire dental arches with no distinct pattern.

Conclusions
The accuracy of semi-automatic prediction of the labial fixed appliance treatment outcome in Class I cases with moderate crowding is not yet sufficient. While average measures showed deviations less than 1 mm, examination of individual color-coded distance maps revealed significant disparities between the simulated and the actual results.
Transcriptome analysis reveals various genes involved in the regulation of potato to late blight
Authors: Zhang Weina , Ma Yifan , Kang Yichen , Zhang Ruyan , Wang Yong , Chen Zhongjian , Yang Xinyu , Jiao Shujuan , Wang Xingxing , Qin Shuhao 
Published: April 2024

Abstract
Background
Potato (Solanum tuberosum L.) production is seriously threatened by the oomycete Phytophthora infestans (P. infestans). However, it remains unclear how the two potato cultivars, Q9 (moderately resistant) and Atl (susceptible), initiate distinct defense responses after inoculation with P. infestans. To uncover the underlying process, we investigated the dynamic gene expression profiles and the functions of the differentially expressed genes (DEGs).

Results
The results showed that the numbers of up-regulated DEGs were 1345, 1063 and 1694 in Q9 and 272, 603 and 2554 in Atl at 1 day post inoculation (dpi), 3 dpi and 5 dpi, respectively. Meanwhile, the down-regulated DEGs were 1557, 1417 and 389 in Q9 and 114, 364 and 2528 in Atl simultaneously. KEGG enrichment analysis revealed that plant-pathogen interaction, phenylpropanoid biosynthesis and MAPK signaling pathway were significantly enriched in Q9 at the later stage. Furthermore, DEGs associated with plant-pathogen interaction and phenylpropanoid biosynthesis showed higher expression levels in Q9 compared to Atl, especially at the later stage. The expressions of eight DEGs were validated by quantitative real-time PCR (qRT-PCR), which further verified the accuracy of the transcriptomics analysis. In addition, DEGs that were exclusively up-regulated and down-regulated in Q9 were analyzed, which may contribute to the resistance of Q9. Transient expression analysis revealed that four DEGs, including StHP1, StMYB2, StHSP3 and StNAC5, exhibited increased tolerance to P. infestans, indicating a positive role in enhancing the resistance of Q9.

Conclusion
Therefore, the DEGs associated with plant-pathogen interaction, phenylpropanoid biosynthesis and MAPK signaling pathway were involved in regulating late blight, and the expression level of the related genes significantly increased in Q9. In addition, StHP1, StHSP3 and the transcription factors, including StMYB2 and StNAC5, played positive roles in improving the resistance of potato Q9 to P. infestans. These findings provide useful information for further understanding the molecular mechanism of potato resistance to late blight. Furthermore, our study identified novel resistance genes that can be used in resistance breeding and functional research.

Graphical abstract
Corneal subbasal nerve plexus reinnervation and stromal cell morphology with different cap thicknesses in small incision lenticule extraction
Authors: Song Yanzheng , Deng Shijing , Lyv Xiaotong , Xu Yushan , Zhang Fengju , Guo Ning 
Published: April 2024

Abstract
Purpose
The corneal cap thickness is a vital parameter designed in small incision lenticule extraction (SMILE). The purpose was to investigate the changes in corneal subbasal nerve plexus (SNP) and stromal cells with different cap thicknesses and evaluate the optimized design for the surgery.

Methods
In this prospective, comparative, non-randomized study, a total of 108 eyes of 54 patients who underwent SMILE were allocated into three groups with different corneal cap thicknesses (110 μm, 120 μm or 130 μm group). The SNP and stromal cell morphological changes obtained from in vivo corneal confocal microscopy (IVCCM) along with their refractive outcomes were collected at 1 week, 1 month, 3 months and 6 months postoperatively. One-way analysis of variance (ANOVA) was used to compare the parameters among the three groups.

Results
The SNPs in the three groups all decreased after surgery and revealed a gradual increasing trend during the 6-month follow-up. The values of the quantitative nerve metrics were significantly lower in the 110 μm group than in the 120 μm and 130 μm groups, especially at 1 week postoperatively. No difference was detected between the 120 μm and 130 μm groups at any time point. Both Langerhans cells and keratocytes were activated after surgery, and the activation was alleviated during the follow-up.

Conclusions
The SMILE surgeries with 110 μm, 120 μm or 130 μm cap thickness design achieved good efficacy, safety, accuracy and stability for moderate to high myopic correction while the thicker corneal cap was more beneficial for corneal nerve regeneration.
Spontaneous complete regression of pancreaticoduodenal artery aneurysms with celiac artery occlusion after aorto-splenic bypass without additional treatment: a case report
Authors: Fujiwara Sho , Kawamura Keiichiro , Nakano Yoshiyuki , Watanabe Tetsuo , Yamashita Hiroshi 
Published: April 2024

Abstract
Background
Pancreaticoduodenal artery aneurysm (PDAA) is a rare, but fatal disease. However, the association between aneurysm size and the risk of rupture remains unclear. There are many options for therapeutic strategies that should be discussed well because the treatment options are often complicated and highly invasive. However, it remains unclear whether additional endovascular therapy is essential for all patients undergoing bypass surgery. Here, we present a case of triple PDAAs with celiac axis occlusion and spontaneous complete regression of inferior PDAAs (IPDAA) after aneurysmectomy of superior PDAA (SPDAA) and aorto-splenic bypass.

Case presentation
A 68-year-old woman presented with one SPDAA and two IPDAAs caused by celiac axis occlusion. Aneurysmectomy for IPDAAs was difficult because of their anatomical location and shape. Therefore, we planned a two-stage hybrid therapy. The patient underwent aorto-splenic bypass and resection of the SPDAA. Follow-up CT was performed to evaluate the IPDAAs before planned endovascular embolization. Spontaneous regression of the IPDAAs and normalized PDA arcade decreased the blood flow in the PDA arcade. The patient is doing well without graft occlusion, and the IPDAAs have completely regressed 7 years after surgery.

Conclusion
Normalization of hyperinflow to the PDA arcade can lead to the regression of PDAA. Potentially, additional endovascular therapy may not be required in all cases when dilation of the PDA improves. However, more cases must be accumulated to establish criteria for predicting the risks of short- and long-term PDAA ruptures.
Additive manufacturing inert gas flow path strategies for multi-laser powder bed fusion systems and their impact on lattice structure mechanical responses
Authors: Philips Sean P. , Tetteh Abigail , Di Prima Matthew A. , Burchi Albert , Porter Daniel A. 
Published: April 2024

AbstractMulti-laser Additive Manufacturing systems hold great potential to increase productivity. However, adding multiple energy sources to a powder bed fusion system requires careful selection of a laser scan and inert gas flow strategy to optimize component performance. In this work, we explore four different laser scan and argon flow strategies on the quasi-static compressive mechanical response of Body Centered Cubic lattices. Three strategies employ a swim lane method where laser pathing tends to progress parallel to argon flow. Method one only uses a single laser while method two uses four, both with the laser path working against the argon flow. The third method uses four lasers, each operating in their own lane like the second method, but the laser pathing progresses with the argon flow. The fourth method has all four lasers operating in quadrants and the laser pathing trends against the argon flow.The single-laser strategy generally had the lowest mechanical responses compared to the other three strategies. A quadrant strategy generally had the highest quasi-static mechanical responses and was at least 25% greater in stiffness, yield force, ultimate force, and energy absorption when compared to the single laser strategy. However, the four-laser swim strategy where the laser pathing tends against the argon flow was found to be statistically similar to the quadrant strategy. It is hypothesized that spatter introduced onto the powder layer from the melt pool and particle entrainment may be worse for laser pathing which trends with the argon flow direction. Additionally, the additional energy added to the build volume helps to mitigate inter-layer cool time which reduces temperature gradients. This shows that multi-laser AM systems have an impact on part performance and potentially shows lattices built with multi-laser AM systems may have certain advantages over single-laser AM systems.
The preventive effect of Gastrodia elata Blume extract on vancomycin-induced acute kidney injury in rats
Authors: Lee Yeon Su , Park Yu Rim , Lee Hyo Bin , Park Hye Joon , Lee Ha Eun , Kim Geon A , Kim Sang-Hoon , Shin Jae-Ho 
Published: April 2024

Abstract
Background
Gastrodia elata Blume (GEB), a traditional medicinal herb, has been reported to have pharmacological effect including protection against liver, neuron and kidney toxicity. However, explanation of its underlying mechanisms remains a great challenge. This study investigated the protective effects of GEB extract on vancomycin (VAN)-induced nephrotoxicity in rats and underlying mechanisms with emphasis on the anti-oxidative stress, anti-inflammation and anti-apoptosis. The male Sprague-Dawley rats were randomly divided three groups: control (CON) group, VAN group and GEB group with duration of 14 days.

Results
The kidney weight and the serum levels of blood urea nitrogen and creatinine in the GEB group were lower than the VAN group. Histological analysis using hematoxylin & eosin and periodic acid Schiff staining revealed pathological changes of the VAN group. Immunohistochemical analysis revealed that the expression levels of N-acetyl-D-glucosaminidase, myeloperoxidase and tumor necrosis factor-alpha in the GEB group were decreased when compared with the VAN group. The number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells, phosphohistone and malondialdehyde levels were lower in the GEB group than VAN group. The levels of total glutathione in the GEB group were higher than the VAN group.

Conclusions
The findings of this study suggested that GEB extract prevents VAN-induced renal tissue damage through anti-oxidation, anti-inflammation and anti-apoptosis.
The potential anticancer effect of bee venom in combination with sorafenib against HepG2 cell lines via induction of apoptosis and autophagy candidate genes
Authors: Nusair Sara A. , Galal Gehan , Radwan Sara M. 
Published: April 2024

Abstract
Background
Hepatocellular carcinoma (HCC) is a severe threat and a main reason for cancer-related deaths around the world. Drug resistance to sorafenib (Sorf), the effective HCC first-line therapy, is very common. A number of natural compounds, notably bee venom (BV), have been claimed to show a great impact against cancer when administered on its own or in conjunction with chemotherapy. Thus, this study aimed to investigate the anticancer effect of BV alone and/or combined with Sorf on HepG2 liver cancer cell lines.

Methods
Both mRNA and protein expressions of Bax, Bcl-2 and Beclin-1 were investigated by quantitative real-time PCR (qPCR) and western blot respectively, to examine the apoptotic and autophagic regulatory effects of BV and Sorf single treatments plus BV/Sorf combination on HepG2 cell lines.

Results
Our findings showed that BV and Sorf had considerable dose-dependent anti-proliferative effects on HepG2 cells whether administered alone or in combination, with the greatest impact for the combined therapies. Single BV and Sorf treatments showed IC50 of 93.21 and 7.28 μg/ml respectively, while combined treatment showed IC50 of 6.73 μg/ml BV + 6.73 μg/ml Sorf. Moreover, both the pro-apoptotic gene Bax and the autophagy-related gene Beclin-1 showed significant up-regulation in their mRNA expression, while the anti-apoptotic Bcl-2 mRNA gene expression showed significant down-regulation after BV/Sorf treatment as compared to either BV or Sorf single treatment. These qPCR results were further confirmed by western blot.

Conclusions
These findings indicate that BV synergistically potentiates the anticancer effect of Sorf on HepG2 cells through induction of apoptotic and autophagic machineries.
Systematic literature review using PRISMA: exploring the influence of service quality and perceived value on satisfaction and intention to continue relationship
Authors: Tedja Budiarto , Al Musadieq Mochammad , Kusumawati Andriani , Yulianto Edy 
Published: April 2024

AbstractThis study aims to develop a systematic review of the influence of Service Quality and Perceived Value on Satisfaction and Intention to Continue the Relationship from an international and empirical perspective. The Preferred Reporting Items for Systematic Reviews and Meta-analyzes (PRISMA) is used as a guideline for systematic literature review to collect data. The selected journal timeframe is from 2008 to 2024, with 22 chosen articles meeting the criteria. Analysis of the selected primary studies reveals that the concepts of Service Quality and Perceived Value can be associated with Satisfaction and Intention to Continue the Relationship. However, an inconsistency was found that there was a significant and insignificant relationship between Perceived Value and Intention to Continue the Relationship, indicating the need for further development to be scientifically verified and to serve as a gap and reference for future researchers to investigate in different research settings. Novelty: Studies related to Intention to Continue the Relationship measured based on Service Quality, Perceived Value, and Satisfaction have been limited. Additionally, this study attempts to develop a more comprehensive concept or model of Intention to Continue the Relationship involving Service Quality, Perceived Value, and Satisfaction.
Chromatin modifiers in human disease: from functional roles to regulatory mechanisms
Authors: Nie Yali , Song Chao , Huang Hong , Mao Shuqing , Ding Kai , Tang Huifang 
Published: April 2024

AbstractThe field of transcriptional regulation has revealed the vital role of chromatin modifiers in human diseases from the beginning of functional exploration to the process of participating in many types of disease regulatory mechanisms. Chromatin modifiers are a class of enzymes that can catalyze the chemical conversion of pyrimidine residues or amino acid residues, including histone modifiers, DNA methyltransferases, and chromatin remodeling complexes. Chromatin modifiers assist in the formation of transcriptional regulatory circuits between transcription factors, enhancers, and promoters by regulating chromatin accessibility and the ability of transcription factors to acquire DNA. This is achieved by recruiting associated proteins and RNA polymerases. They modify the physical contact between cis-regulatory factor elements, transcription factors, and chromatin DNA to influence transcriptional regulatory processes. Then, abnormal chromatin perturbations can impair the homeostasis of organs, tissues, and cells, leading to diseases. The review offers a comprehensive elucidation on the function and regulatory mechanism of chromatin modifiers, thereby highlighting their indispensability in the development of diseases. Furthermore, this underscores the potential of chromatin modifiers as biomarkers, which may enable early disease diagnosis. With the aid of this paper, a deeper understanding of the role of chromatin modifiers in the pathogenesis of diseases can be gained, which could help in devising effective diagnostic and therapeutic interventions.
Association Between Body Composition and Survival in Patients With Gastroesophageal Adenocarcinoma: An Automated Deep Learning Approach
Authors: Jung Matthias , Diallo Thierno D. , Scheef Tobias , Reisert Marco , Rau Alexander , Russe Maximilan F. , Bamberg Fabian , Fichtner-Feigl Stefan , Quante Michael , Weiss Jakob 
Published: April 2024

PURPOSE Body composition (BC) may play a role in outcome prognostication in patients with gastroesophageal adenocarcinoma (GEAC). Artificial intelligence provides new possibilities to opportunistically quantify BC from computed tomography (CT) scans. We developed a deep learning (DL) model for fully automatic BC quantification on routine staging CTs and determined its prognostic role in a clinical cohort of patients with GEAC. MATERIALS AND METHODS We developed and tested a DL model to quantify BC measures defined as subcutaneous and visceral adipose tissue (VAT) and skeletal muscle on routine CT and investigated their prognostic value in a cohort of patients with GEAC using baseline, 3-6-month, and 6-12-month postoperative CTs. Primary outcome was all-cause mortality, and secondary outcome was disease-free survival (DFS). Cox regression assessed the association between (1) BC at baseline and mortality and (2) the decrease in BC between baseline and follow-up scans and mortality/DFS. RESULTS Model performance was high with Dice coefficients ≥0.94 ± 0.06. Among 299 patients with GEAC (age 63.0 ± 10.7 years; 19.4% female), 140 deaths (47%) occurred over a median follow-up of 31.3 months. At baseline, no BC measure was associated with DFS. Only a substantial decrease in VAT >70% after a 6- to 12-month follow-up was associated with mortality (hazard ratio [HR], 1.99 [95% CI, 1.18 to 3.34]; P = .009) and DFS (HR, 1.73 [95% CI, 1.01 to 2.95]; P = .045) independent of age, sex, BMI, Union for International Cancer Control stage, histologic grading, resection status, neoadjuvant therapy, and time between surgery and follow-up CT. CONCLUSION DL enables opportunistic estimation of BC from routine staging CT to quantify prognostic information. In patients with GEAC, only a substantial decrease of VAT 6-12 months postsurgery was an independent predictor for DFS beyond traditional risk factors, which may help to identify individuals at high risk who go otherwise unnoticed.
Augmin complex activity finetunes dendrite morphology through non-centrosomal microtubule nucleation in vivo
Authors: Zhang Yun , Sung Hsin-Ho , Ziegler Anna B. , Wu Ying-Chieh , Viais Ricardo , Sánchez-Huertas Carlos , Kilo Lukas , Agircan Fikret Gürkan , Cheng Ying-Ju , Mouri Kousuke , Uemura Tadashi , Lüders Jens , Chien Cheng-Ting , Tavosanis Gaia 
Published: April 2024

ABSTRACT
During development, neurons achieve a stereotyped neuron type-specific morphology, which relies on dynamic support by microtubules (MTs). An important player is the augmin complex (hereafter augmin), which binds to existing MT filaments and recruits the γ-tubulin ring complex (γ-TuRC), to form branched MTs. In cultured neurons, augmin is important for neurite formation. However, little is known about the role of augmin during neurite formation in vivo. Here, we have revisited the role of mammalian augmin in culture and then turned towards the class four Drosophila dendritic arborization (c4da) neurons. We show that MT density is maintained through augmin in cooperation with the γ-TuRC in vivo. Mutant c4da neurons show a reduction of newly emerging higher-order dendritic branches and in turn also a reduced number of their characteristic space-filling higher-order branchlets. Taken together, our data reveal a cooperative function for augmin with the γ-TuRC in forming enough MTs needed for the appropriate differentiation of morphologically complex dendrites in vivo.