bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid imaging of intravenous gadolinium-based contrast agent (GBCA) entering ventricular cerebrospinal fluid (CSF) through the choroid plexus in healthy human subjects
Authors: Sun Yuanqi , Cao Di , Pillai Jay J. , Paez Adrian , Li Yinghao , Gu Chunming , Pogson Jacob M. , Knutsson Linda , Barker Peter B. , van Zijl Peter C. M. , Bakker Arnold , Ward Bryan K. , Hua Jun 
Published: September 2024

Abstract
Background
Pathways for intravenously administered gadolinium-based-contrast-agents (GBCAs) entering cerebrospinal-fluid (CSF) circulation in the human brain are not well-understood. The blood-CSF-barrier (BCSFB) in choroid-plexus (CP) has long been hypothesized to be a main entry-point for intravenous-GBCAs into CSF. Most existing studies on this topic were performed in animals and human patients with various diseases. Results in healthy human subjects are limited. Besides, most studies were performed using MRI methods with limited temporal resolution and significant partial-volume effects from blood and CSF.

Methods
This study employs the recently developed dynamic-susceptibility-contrast-in-the-CSF (cDSC) MRI approach to measure GBCA-distribution in the CSF immediately and 4 h after intravenous-GBCA administration in healthy subjects. With a temporal resolution of 10 s, cDSC MRI can track GBCA-induced CSF signal changes during the bolus phase, which has not been investigated previously. It employs a long echo-time (TE = 1347 ms) to suppress tissue and blood signals so that pure CSF signal is detected with minimal partial-volume effects. GBCA concentration in the CSF can be estimated from cDSC MRI. In this study, cDSC and FLAIR MRI were performed immediately and 4 h after intravenous GBCA administration in 25 healthy volunteers (age 48.9 ± 19.5 years; 14 females). Paired t-tests were used to compare pre-GBCA and post-GBCA signal changes, and their correlations with age were evaluated using Pearson-correlation-coefficients.

Results
At ~ 20 s post-GBCA, GBCA-induced cDSC signal changes were detected in the CSF around CP (ΔS/S = − 2.40 ± 0.30%; P < .001) but not in the rest of lateral ventricle (LV). At 4 h, significant GBCA-induced cDSC signal changes were observed in the entire LV (ΔS/S = − 7.58 ± 3.90%; P = .002). FLAIR MRI showed a similar trend. GBCA-induced CSF signal changes did not correlate with age.

Conclusions
These results provided direct imaging evidence that GBCAs can pass the BCSFB in the CP and enter ventricular CSF immediately after intravenous administration in healthy human brains. Besides, our results in healthy subjects established a basis for clinical studies in brain diseases exploiting GBCA-enhanced MRI to detect BCSFB dysfunction.
Individualized C1-2 intra-articular three-dimensional printed porous titanium alloy cage for craniovertebral deformity
Authors: Jian Qiang , Qin Shaw , Hou Zhe , Zhao Xingang , Liang Cong , Fan Tao 
Published: September 2024

Abstract
Background
Congenital craniovertebral deformity, including basilar invagination (BI) and atlantoaxial instability (AAI), are often associated with three-dimensional (3D) deformity, such as C1-2 rotational deformity, craniocervical kyphosis, C1 lateral inclination, among other abnormalities. Effective management of these conditions requires the restoration of the 3D alignment to achieve optimal reduction. Recently, 3D printing technology has emerged as a valuable tool in spine surgery, offering the significant advantage of allowing surgeons to customize the prosthesis design. This innovation provides an ideal solution for precise 3D reduction in the treatment of craniovertebral deformities.

Objective
This study aims to describe our approach to individualized computer-simulated reduction and the design of C1-2 intra-articular 3D printed porous titanium alloy cages for the quantitative correction of craniovertebral junction deformities.

Methods
A retrospective analysis was conducted on patients with craniovertebral deformities treated at our institution using individualized 3D-printed porous titanium alloy cages. Preoperative CT data were used to construct models for 3D realignment simulations. Cage designs were tailored to the simulated joint morphology following computer-assisted realignment. Preoperative and postoperative parameters were statistically analyzed.

Results
Fourteen patients were included in the study, with a total of 28 3D-printed porous titanium alloy cages implanted. There were no cases of C2 nerve root resection or vertebral artery injury. All patients experienced symptom relief and stable implant fixation achieved in all cases. No implant-related complications were reported.

Conclusion
The use of individualized computer-simulated reduction and the design of C1-2 intra-articular 3D printed porous titanium alloy cage facilitates precise 3D realignment in patients with craniovertebral deformities, demonstrating effectiveness in symptom relief and stability.
Proteasome inhibition enhances the anti-leukemic efficacy of chimeric antigen receptor (CAR) expressing NK cells against acute myeloid leukemia
Authors: Sedloev David , Chen Qian , Unglaub Julia M. , Schanda Nicola , Hao Yao , Besiridou Eleni , Neuber Brigitte , Schmitt Anita , Raffel Simon , Liu Yi , Janssen Maike , Müller-Tidow Carsten , Schmitt Michael , Sauer Tim 
Published: September 2024

Abstract
Background
Relapsed and refractory acute myeloid leukemia (AML) carries a dismal prognosis. CAR T cells have shown limited efficacy in AML, partially due to dysfunctional autologous T cells and the extended time for generation of patient specific CAR T cells. Allogeneic NK cell therapy is a promising alternative, but strategies to enhance efficacy and persistence may be necessary. Proteasome inhibitors (PI) induce changes in the surface proteome which may render malignant cells more vulnerable to NK mediated cytotoxicity. Here, we investigated the potential benefit of combining PIs with CAR-expressing allogeneic NK cells against AML.

Methods
We established the IC50 concentrations for Bortezomib and Carfilzomib against several AML cell lines. Surface expression of class-I HLA molecules and stress-associated proteins upon treatment with proteasome inhibitors was determined by multiparameter flow cytometry. Using functional in vitro assays, we explored the therapeutic synergy between pre-treatment with PIs and the anti-leukemic efficacy of NK cells with or without expression of AML-specific CAR constructs against AML cell lines and primary patient samples. Also, we investigated the tolerability and efficacy of a single PI application strategy followed by (CAR-) NK cell infusion in two different murine xenograft models of AML.

Results
AML cell lines and primary AML patient samples were susceptible to Bortezomib and Carfilzomib mediated cytotoxicity. Conditioned resistance to Azacitidine/Venetoclax did not confer primary resistance to PIs. Treating AML cells with PIs reduced the surface expression of class-I HLA molecules on AML cells in a time-and-dose dependent manner. Stress-associated proteins were upregulated on the transcriptional level and on the cell surface. NK cell mediated killing of AML cells was enhanced in a synergistic manner. PI pre-treatment increased effector-target cell conjugate formation and Interferon-γ secretion, resulting in enhanced NK cell activity against AML cell lines and primary samples in vitro. Expression of CD33- and CD70-specific CARs further improved the antileukemic efficacy. In vivo, Bortezomib pre-treatment followed by CAR-NK cell infusion reduced AML growth, leading to prolonged overall survival.

Conclusions
PIs enhance the anti-leukemic efficacy of CAR-expressing allogeneic NK cells against AML in vitro and in vivo, warranting further exploration of this combinatorial treatment within early phase clinical trials.
Safety and efficacy of topical testosterone in breast cancer patients receiving ovarian suppression and aromatase inhibitor therapy
Authors: Taranto Patrícia , de Brito Sales Diogo , Maluf Fernando Cotait , Guendelmann Rafael Aliosha Kaliks , de Melo Pompei Luciano , Leal Alessandro , Buzaid Antonio Carlos , Schvartsman Gustavo 
Published: September 2024

Abstract
Background
Premenopausal, high-risk, hormone receptor-positive breast cancer patients are often treated with ovarian suppression in combination with aromatase inhibitors (AI). This combination has important adverse effects, particularly in sexual function, such as vaginal dryness and loss of libido. There is no effective therapy for reduced sexual function in this setting. Our study aimed to determine the efficacy and safety, particularly regarding sexual function, of a low-dose, topical testosterone gel administration.

Methods
This is a pilot, single-center study, designed to evaluate the efficacy of topical testosterone gel (3 mg/day) in improving sexual function in 29 premenopausal patients on ovarian suppression in combination with an AI. The primary safety endpoint was to assess serum estradiol elevation. The primary efficacy endpoint was sexual function improvement, assessed by the Female Sexual Function Index questionnaire.

Results
We report the results on 29 patients. Twenty-two patients (75%) completed the 3-month treatment, and seven discontinued treatment before completion, mostly due to logistical difficulties related to the COVID-19 pandemic. All patients maintained the value of baseline mass spectrometry assay for estradiol of less than 2.7 pg/mL during the undertaken measurements. We observed a significant improvement in Female Sexual Function Index measures over the visits, with an increase from a mean of 11.7 at baseline to 19.1 in the third month (p < 0.001), with the greatest improvement observed between the second and third months.

Conclusions
Our findings suggest that topical testosterone seems to be safe and may be effective in improving sexual function in patients on ovarian suppression and AI.

Trial registration
The project was submitted and approved through the hospital’s SGPP platform in 11/26/2019 (Project No. SGPP 393819) and CAAE (Research Ethics Committee) (CAAE No 25609719.5.0000.007).
Medial temporal lobe atrophy patterns in early-versus late-onset amnestic Alzheimer’s disease
Authors: Wuestefeld Anika , Pichet Binette Alexa , van Westen Danielle , Strandberg Olof , Stomrud Erik , Mattsson-Carlgren Niklas , Janelidze Shorena , Smith Ruben , Palmqvist Sebastian , Baumeister Hannah , Berron David , Yushkevich Paul A. , Hansson Oskar , Spotorno Nicola , Wisse Laura E.M. 
Published: September 2024

Abstract
Background
The medial temporal lobe (MTL) is hypothesized to be relatively spared in early-onset Alzheimer’s disease (EOAD). Yet, detailed examination of MTL subfields and drivers of atrophy in amnestic EOAD is lacking.

Methods
BioFINDER-2 participants with memory impairment, abnormal amyloid-β and tau-PET were included. Forty-one amnestic EOAD individuals ≤65 years and, as comparison, late-onset AD (aLOAD, ≥70 years, n = 154) and amyloid-β-negative cognitively unimpaired controls were included. MTL subregions and biomarkers of (co-)pathologies were measured.

Results
AD groups showed smaller MTL subregions compared to controls. Atrophy patterns were similar across AD groups: aLOAD showed thinner entorhinal cortices than aEOAD; aEOAD showed thinner parietal regions than aLOAD. aEOAD showed lower white matter hyperintensities than aLOAD. No differences in MTL tau-PET or transactive response DNA binding protein 43-proxy positivity were found.

Conclusions
We found evidence for MTL atrophy in amnestic EOAD and overall similar levels to aLOAD of MTL tau pathology and co-pathologies.
Review on effect of fermentation on physicochemical properties, anti-nutritional factors and sensory properties of cereal-based fermented foods and beverages
Authors: Kitessa Daniel Asfaw 
Published: September 2024

AbstractFermentation is the oldest biotechnology in which a metabolic process carried out without the involvement of oxygen. It is one of the food processing methods that improve the nutrient contents and sensorial properties with potentially reducing or eliminating pathogenic microorganisms and natural toxins. The aim of this review is to compare, contrast and summarize the scientific data on the effect of fermentation on physicochemical properties, anti-nutritional factors and sensory properties of cereal-based fermented foods and beverages. The results of this review showed that fermentation improves the nutritional value of some proximate composition such as crude protein and fat contents, while decreases the carbohydrate and crude fiber contents. It also improves the bioavailability, antioxidant activities and sensory properties of cereal-based foods and beverages. This review concluded that fermentation improves the nutritional quality of proximate composition, bioavailability of minerals and phytochemicals, and decrease the anti-nutritional factors of cereal-based fermented foods and beverages.
Application and insights of targeted next-generation sequencing in a large cohort of 46,XY disorders of sex development in Chinese
Authors: Chen Hongyu , Chen Guangjie , Li Fengxia , Huang Yong , Zhu Linfeng , Zhao Yijun , Jiang Ziyi , Yan Xiang , Yu Lan 
Published: September 2024

Abstract
Purpose
46,XY disorders of sex development (46,XY DSD) are characterized by incomplete masculinization of genitalia with reduced androgenization. Accurate clinical management remains challenging, especially based solely on physical examination. Targeted next-generation sequencing (NGS) with known pathogenic genes provides a powerful tool for diagnosis efficiency. This study aims to identify the prevalent genetic variants by targeted NGS technology and investigate the diagnostic rate in a large cohort of 46,XY DSD patients, with most of them presenting atypical phenotypes.

Methods
Two different DSD panels were developed for sequencing purposes, targeting a cohort of 402 patients diagnosed with 46,XY DSD, who were recruited from the Department of Urology at Children’s Hospital, Zhejiang University School of Medicine (Hangzhou, China). The detailed clinical characteristics were evaluated, and peripheral blood was collected for targeted panels to find the patients’ variants. The clinical significance of these variants was annotated according to American College of Medical Genetics and Genomics (ACMG) guidelines.

Results
A total of 108 variants across 42 genes were found in 107 patients, including 46 pathogenic or likely pathogenic variants, with 45.7%(21/46) being novel. Among these genes, SRD5A2, AR, FGFR1, LHCGR, NR5A1, CHD7 were the most frequently observed. Besides, we also detected some uncommon causative genes like SOS1, and GNAS. Oligogenic variants were also identified in 9 patients, including several combinations PROKR2/FGFR1/CYP11B1, PROKR2/ATRX, PROKR2/AR, FGFR1/LHCGR/POR, FGFR1/NR5A1, GATA4/NR5A1, WNT4/AR, MAP3K1/FOXL2, WNT4/AR, and SOS1/FOXL2.

Conclusion
The overall genetic diagnostic rate was 11.2%(45/402), with an additional 15.4% (62/402) having variants of uncertain significance. Additionally, trio/duo patients had a higher genetic diagnostic rate (13.4%) compared to singletons (8.6%), with a higher proportion of singletons (15.1%) presenting variants of uncertain significance. In conclusion, targeted gene panels identified pathogenic variants in a Chinese 46,XY DSD cohort, expanding the genetic understanding and providing evidence for known pathogenic genes’ involvement.
Fast 3D solvers for interactive computational mechanics
Authors: Gavranovic Stefan , Hassan Zain , Failer Lukas , Hartmann Dirk 
Published: September 2024

AbstractWhile interactive simulations have been mostly limited to Computer Graphics applications, new generations of Graphics Processing Units (GPUs) allow the realization of industrial-grade interactive 3D physics simulations. By combining an immersed boundary method with efficient GPU-based MINRES and CG solvers using a GPU-based geometric multigrid preconditioner, we demonstrate a fast industrial 3D computational mechanics solver. The various implementation aspects - specifically how they differ from similar concepts used in the Computer Graphics community - are discussed in detail. The proposed concept opens up new classes of industrial simulation applications allowing a democratization beyond today’s expert users, from designer centric simulation to operational and service decisions based on 3D simulations. To support this, we provide various benchmark cases including a real-world study of a simulation-based service decision for a damaged gear-box mount.
Artificial intelligence (AI) -integrated educational applications and college students’ creativity and academic emotions: students and teachers’ perceptions and attitudes
Authors: Lin Haozhuo , Chen Qiu 
Published: September 2024

Abstract
Background
Integrating Artificial Intelligence (AI) in educational applications is becoming increasingly prevalent, bringing opportunities and challenges to the learning environment. While AI applications have the potential to enhance structured learning, they may also significantly impact students’ creativity and academic emotions.

Objectives
This study aims to explore the effects of AI-integrated educational applications on college students’ creativity and academic emotions from the perspectives of both students and teachers. It also assessed undergraduate students’ and faculty’s attitudes to AI-integrated applications.

Methodology
A mixed-method research design was used. In the first phase, a qualitative research approach was employed, utilizing theoretical sampling to select informants. Data were collected through in-depth interviews with undergraduate students and university lecturers to gain comprehensive insights into their experiences and perceptions. A scale was developed, validated, and administered to 120 students and faculty in the quantitative phase. Descriptive statistics was used to analyze the data.

Findings
The study revealed that AI applications often impose rigid frameworks that constrain creative thinking and innovation, leading to emotional disengagement due to AI interactions’ repetitive and impersonal nature. Additionally, constant AI assessments heightened performance anxiety, and technical frustrations disrupted the learning process. Conversely, AI applications stimulated creativity by introducing new ideas and problem-solving techniques, enhanced engagement through interactive elements, provided personalized feedback, and supported emotional well-being with gamified elements and constant availability. Quantitative data also verified that teachers and students have positive attitudes toward the benefits and challenges of these applications.

Conclusions
AI integration in educational applications has a dual-edged impact on college students’ creativity and academic emotions. While there are notable benefits in stimulating creativity and enhancing engagement, significant challenges such as creativity constraints, emotional disengagement, and performance anxiety must be addressed. Balancing these factors requires thoughtful implementation and continuous evaluation to optimize the role of AI in education.
Radiomics predicts the prognosis of patients with clear cell renal cell carcinoma by reflecting the tumor heterogeneity and microenvironment
Authors: Wu Ji , Li Jian , Huang Bo , Dong Sunbin , Wu Luyang , Shen Xiping , Zheng Zhigang 
Published: September 2024

Abstract
Purpose
We aimed to develop and externally validate a CT-based deep learning radiomics model for predicting overall survival (OS) in clear cell renal cell carcinoma (ccRCC) patients, and investigate the association of radiomics with tumor heterogeneity and microenvironment.

Methods
The clinicopathological data and contrast-enhanced CT images of 512 ccRCC patients from three institutions were collected. A total of 3566 deep learning radiomics features were extracted from 3D regions of interest. We generated the deep learning radiomics score (DLRS), and validated this score using an external cohort from TCIA. Patients were divided into high and low-score groups by the DLRS. Sequencing data from the corresponding TCGA cohort were used to reveal the differences of tumor heterogeneity and microenvironment between different radiomics score groups. What’s more, univariate and multivariate Cox regression were used to identify independent risk factors of poor OS after operation. A combined model was developed by incorporating the DLRS and clinicopathological features. The SHapley Additive exPlanation method was used for interpretation of predictive results.

Results
At multivariate Cox regression analysis, the DLRS was identified as an independent risk factor of poor OS. The genomic landscape of different radiomics score groups was investigated. The heterogeneity of tumor cell and tumor microenvironment significantly varied between both groups. In the test cohort, the combined model had a great predictive performance, with AUCs (95%CI) for 1, 3 and 5-year OS of 0.879(0.868–0.931), 0.854(0.819–0.899) and 0.831(0.813–0.868), respectively. There was a significant difference in survival time between different groups stratified by the combined model. This model showed great discrimination and calibration, outperforming the existing prognostic models (all p values < 0.05).

Conclusion
The combined model allowed for the prognostic prediction of ccRCC patients by incorporating the DLRS and significant clinicopathologic features. The radiomics features could reflect the tumor heterogeneity and microenvironment.
Tryptophanyl tRNA synthetase is an alternative synovial biomarker for diagnosis of septic arthritis in knee joint
Authors: Lee Byung Hoon , Na Young Gon , Ham Seong Hyup , Jin Mirim , Kim Yoon Tae , Kim Kyung-Ok , Sim Jae Ang 
Published: September 2024

Abstract
Background
To evaluate the diagnostic characteristics of tryptophanyl tRNA synthetase (WRS) for the diagnosis of septic arthritis of the knee joint and to determine whether it is a reliable and sensitive synovial biomarker for discriminating septic arthritis from other types of arthritis.

Methods
Patients joint effusions for which septic arthritis was suspected were prospectively recruited between January 2019 and September 2020. A total of 9 patients had septic arthritis, 6 had acute gout attack, 1 had an acute flare of chronic rheumatic arthritis, and 46 had pseudogout or reactive arthropathy. Traditional inflammatory markers were measured, and their diagnostic abilities were compared. Neutrophil count, C-reactive protein (CRP) level, WRS, and human neutrophil α-defensin levels were assessed in the synovial fluids. Demographic parameters and biomarkers with a P < 0.05 in differentiating septic from nonseptic arthritis were included in a multivariable model. A multivariable logistic regression with a stepwise selection was performed to build the final combined model. Receiver operating characteristic curves were used to establish optimal thresholds for the diagnosis of septic arthritis of the knee joint, and the area under the curve was calculated to determine the overall accuracy of these tests compared with patients with nonseptic inflammatory arthritis.

Results
Patients with septic arthritis were more likely to display higher serum WBC and CRP levels, synovial neutrophil counts, and levels of two synovial biomarkers, including WRS and α-defensin. WRS showed the highest specificity (87.5%) and sensitivity (83.3%) with α-defensin among the three synovial biomarkers.

Conclusions
Synovial fluid WRS is a relevant biomarker in discriminating septic arthritis from other inflammatory arthritis and should be tested in an independent cohort.
Level of evidence: prospective observational study, III.