bluuebunny/crossref_metadata_2025_split huggingface dataset:
The ex vivo perfused mouse adrenal gland—a new model to study aldosterone secretion
Authors: Plain Allein , Knödl Laura , Tegtmeier Ines , Bandulik Sascha , Warth Richard 
Published: March 2024

AbstractAldosterone is a steroid hormone that is important for maintaining the volume and ionic composition of extracellular fluids and is produced in the zona glomerulosa of the adrenal cortex. The basic mechanisms controlling aldosterone secretion are known. However, more detailed studies on the regulation of aldosterone secretion often fail due to the lack of suitable models: although secretion can be studied in cultured adrenocortical cells under defined conditions, the differentiation status of the cells is difficult to control and the complex anatomy of the adrenal cortex is lost. In living animals, the physiological context is intact, but the influences are manifold and the examination conditions cannot be sufficiently controlled. One method that closes the gap between cell models and studies in living animals is the isolated perfused adrenal gland. In the past, this method has provided important data on the pathophysiology of adrenal glands from larger animals, but the technique was not used in mice. Here, we developed a method for isolation and perfusion of the mouse adrenal gland to study aldosterone secretion. This technique preserves the complex anatomical and functional context of the mouse adrenal cortex, to ensure defined experimental conditions and to minimize extra-adrenal influences. Initial series of experiments with the ex vivo perfused mouse adrenal gland show that this model offers the possibility for unique insights into pathophysiological regulatory principles and is suitable for the use of genetically modified mouse models.
Hydroxy(phenyl)pyruvic acid reductase in Actaea racemosa L.: a putative enzyme in cimicifugic and fukinolic acid biosynthesis
Authors: Jahn Anne , Petersen Maike 
Published: March 2024

Abstract
Main conclusion
Hydroxy(phenyl)pyruvic acid reductase from Actaea racemosa catalyzes dual reactions in reducing 4-hydroxyphenylpyruvic acid as well as β-hydroxypyruvic acid. It thus qualifies to be part of fukinolic and cimicifugic acid biosynthesis and also photorespiration.

Abstract
The accumulation of fukinolic acid and cimicifugic acids is mainly restricted to Actaea racemosa (Ranunculaceae) and other species of the genus Actaea/Cimicifuga. Cimicifugic and fukinolic acids are composed of a hydroxycinnamic acid part esterified with a benzyltartaric acid moiety. The biosynthesis of the latter is unclear. We isolated cDNA encoding a hydroxy(phenyl)pyruvic acid reductase (GenBank OR393286) from suspension-cultured material of A. racemosa (ArH(P)PR) and expressed it in E. coli for protein production. The heterologously synthesized enzyme had a mass of 36.51 kDa and catalyzed the NAD(P)H-dependent reduction of 4-hydroxyphenylpyruvic acid to 4-hydroxyphenyllactic acid or β-hydroxypyruvic acid to glyceric acid, respectively. The optimal temperature was at 38 °C and the pH optimum at pH 7.5. NADPH is the preferred cosubstrate (Km 23 ± 4 µM). Several substrates are accepted by ArH(P)PR with β-hydroxypyruvic acid (Km 0.26 ± 0.12 mM) followed by 4-hydroxyphenylpyruvic acid (Km 1.13 ± 0.12 mM) as the best ones. Thus, ArH(P)PR has properties of β-hydroxypyruvic acid reductase (involved in photorespiration) as well as hydroxyphenylpyruvic acid reductase (possibly involved in benzyltartaric acid formation).
Resveratrol ameliorates glioblastoma inflammatory response by reducing NLRP3 inflammasome activation through inhibition of the JAK2/STAT3 pathway
Authors: Zhang Chao , Peng Qian , Tang Yuhang , Wang Chengcheng , Wang Shuai , Yu Dong , Hou Shiqiang , Wang Yu , Zhang Lanlan , Lin Ning 
Published: March 2024

Abstract
Objectives
The aim of this study was to investigate the anti-tumor effect of resveratrol (RSV) on glioblastoma (GBM) and its specific mechanism in improving the inflammatory response of the tumor microenvironment. The tumor microenvironment of GBM is highly neuroinflammatory, inducing tumor immunosuppression. Therefore, ameliorating the inflammatory response is an important focus for anti-tumor research.

Methods
The anti-tumor effect of RSV on GBM was demonstrated through in vitro cellular assays, including CCK-8, EdU, PI staining, Transwell, wound healing assay, and flow cytometry. Potential mechanisms of RSV's anti-GBM effects were identified through network pharmacological analysis. In addition, the relationship of RSV with the JAK2/STAT3 signaling pathway and the inflammasome NLRP3 was verified using Western blot.

Results
RSV significantly inhibited cell viability in GBM cell lines LN-229 and U87-MG. Furthermore, it inhibited the proliferation and invasive migration ability of GBM cells, while promoting apoptosis. Network pharmacological analysis revealed a close association between the anti-GBM effects of RSV and the JAK/STAT signaling pathway, as well as inflammatory responses. Western blot analysis confirmed that RSV inhibited the over-activation of the inflammasome NLRP3 through the JAK2/STAT3 signaling pathway. Partial reversal of RSV's inhibition of inflammasome NLRP3 was observed with the addition of the JAK/STAT agonist RO8191.

Conclusions
In vitro, RSV can exert anti-tumor effects on GBM and improve the inflammatory response in the GBM microenvironment by inhibiting the activation of the JAK2/STAT3 signaling pathway. These findings provide new insights into potential therapeutic targets for GBM.
Urocortin-1 promotes colorectal cancer cell migration and proliferation and inhibits apoptosis via inhibition of the p53 signaling pathway
Authors: Guo Xiaolan , Li Ya , Chen Xiangyu , Sun Binghua , Guo Xiaolan 
Published: March 2024

Abstract
Purpose
To investigate the effect of urocortin-1 (UCN-1) on growth, migration, and apoptosis in colorectal cancer (CRC) in vivo and vitro and the mechanism by which UCN-1 modulates CRC cells in vitro.

Methods
The correlation between UCN-1 and CRC was evaluated using The Cancer Genome Atlas (TCGA) database and a tissue microarray. The expression of UCN-1 in CRC cells was assessed using quantitative real-time polymerase chain reaction (RT-qPCR) and western blotting. In vitro, the influence of UCN-1 on the proliferation, apoptosis, and migration of HT-29, HCT-116, and RKO cells was explored using the celigo cell counting assay or cell counting kit-8 (CCK8), flow cytometry, and wound healing or Transwell assays, respectively. In vivo, the effect of UCN-1 on CRC growth and progression was evaluated in nude mice. The downstream pathway underlying UCN-1-mediated regulation of CRC was determined using the phospho-kinase profiler array in RKO cells. Lentiviruses were used to knockdown or upregulate UCN-1 expression in cells.

Results
Both the TCGA and tissue microarray results showed that UCN-1 was strongly expressed in the tissues of patients with CRC. Furthermore, the tissue microarray results showed that the expression of UCN-1 was higher in male than in female patients, and high expression of UCN-1 was associated with higher risk of lymphatic metastasis and later pathological stage. UCN-1 knockdown caused a reduction in CRC cell proliferation, migration, and colony formation, as well as an increase in apoptosis. In xenograft experiments, tumors generated from RKO cells with UCN-1 knockdown exhibited reduced volumes and weights. A reduction in the expression of Ki-67 in xenograft tumors indicated that UCN-1 knockdown curbed tumor growth. The human phospho-kinase array showed that the p53 signaling pathway participated in UCN-1-mediated CRC development. The suppression in migration and proliferation caused by UCN-1 knockdown was reversed by inhibitors of p53 signal pathway, while the increase in cell apoptosis was suppressed. On the other hand, overexpression of UCN-1 promoted proliferation and migration and inhibited apoptosis in CRC cells. Overexpression of p53 reversed the effect of UCN-1 overexpression on CRC development.

Conclusion
UCN-1 promotes migration and proliferation and inhibits apoptosis via inhibition of the p53 signaling pathway.
Rahmenbedingungen einer Forschungsethik der datenintensiven medizinischen Forschung
Authors: Wiesing Urban , Funer Florian 
Published: March 2024

ZusammenfassungDie Forschungs- und Regulierungsebene bei datenintensiver Forschung in der Medizin liegen auseinander. Ein heterogenes Feld aus regulierenden Institutionen mit regional ungleichen Regelungen, sowohl hinsichtlich der Dichte als auch der Restriktivität von Regelungen, steht einer globalen Entwicklung der Technologien entgegen. Trotz oder gerade wegen mangelnder global-gültiger Regulierungen können auch unverbindliche oder nur bedingt verbindliche normative Vorgaben der Orientierung dienen. Doch wie soll eine solche normative Regulierung angesichts datenintensiver Forschung in der Medizin ausgestaltet werden und woran soll sie sich orientieren? Die Frage, wie konkret und detailliert man eine solche Forschung regulieren sollte, lässt sich nur im Einzelfall für bestimmte Situationen und Institutionen beantworten. Ob dabei neue Normen oder Gewichtungen von Normen vorgenommen werden sollen, oder ob die Normen und deren Gewichtung weiterhin bestehen bleiben sollen, lässt sich nur mit Verweis auf starke normative Argumente beantworten. An zwingenden Argumenten für neue Normen angesichts der datenintensiven medizinischen Forschung mangelt es bisher. Dennoch ist eine Umsetzungsarbeit von Normen, egal ob neue oder alte, und deren Anwendung auf eine neue Methode oder Technologie allemal zu erbringen. Es bedarf daher – wie schon bisher – beider: sowohl etablierter und transparent kommunizierter Normen als auch des unabhängigen Urteils zur Anwendung dieser Normen. Angesichts der besonderen Eignung für diese Aufgabe sollten auch weiterhin Ethik-Kommissionen als prozedurale Instanz bei der Bewilligung von datenintensiver Forschung in der Medizin gefordert und befähigt werden, die als unabhängige Institution ein Urteil im Einzelfall anhand vorgegebener Normen fällen. Nichtsdestotrotz können sich die veränderten Praktiken datenintensiver Forschungsprojekte auch in neuen Anforderungen an Ethik-Kommissionen niederschlagen, denen mit Reformen der Arbeitsweise begegnet werden sollte.
Learn & drop: fast learning of cnns based on layer dropping
Authors: Cruciata Giorgio , Cruciata Luca , Lo Presti Liliana , van Gemert Jan , La Cascia Marco 
Published: March 2024

AbstractThis paper proposes a new method to improve the training efficiency of deep convolutional neural networks. During training, the method evaluates scores to measure how much each layer’s parameters change and whether the layer will continue learning or not. Based on these scores, the network is scaled down such that the number of parameters to be learned is reduced, yielding a speed-up in training. Unlike state-of-the-art methods that try to compress the network to be used in the inference phase or to limit the number of operations performed in the back-propagation phase, the proposed method is novel in that it focuses on reducing the number of operations performed by the network in the forward propagation during training. The proposed training strategy has been validated on two widely used architecture families: VGG and ResNet. Experiments on MNIST, CIFAR-10 and Imagenette show that, with the proposed method, the training time of the models is more than halved without significantly impacting accuracy. The FLOPs reduction in the forward propagation during training ranges from 17.83% for VGG-11 to 83.74% for ResNet-152. As for the accuracy, the impact depends on the depth of the model and the decrease is between 0.26% and 2.38% for VGGs and between 0.4 and 3.2% for ResNets. These results demonstrate the effectiveness of the proposed technique in speeding up learning of CNNs. The technique will be especially useful in applications where fine-tuning or online training of convolutional models is required, for instance because data arrive sequentially.
Detection of multitask mental workload using gamma band power features
Authors: Korkmaz Onur Erdem , Korkmaz Sevde Gül , Aydemir Onder 
Published: March 2024

AbstractCognitive fatigue occurs in various situations and is an essential condition to detect. In this study, how single and multi-tasking tests affect cognitive workload was examined, and multi-tasking was detected using electroencephalography (EEG) signals. In the cognitive workload paradigm, single-task tests with blocks 1 and 2 and multi-tasking tests with block 3 were created. EEG signals obtained from these blocks were treated as different frequency bands and lengths, and binary classification was performed. Two binary classifications were made: block 1–block 3 and block 2–block 3. According to the results, the highest classification accuracy for block 1–block 3 was obtained as 97.11% using the gamma frequency band and 5-s EEG length. For block 2–block 3, the highest classification accuracy was obtained as 90.88% using the gamma frequency band and 5-s EEG length. As a result, this study distinguished multi-tasking and single task with high classification accuracy. The developed model can be used to detect attention deficit and inability to focus. In addressing the prevalent challenges of distinguishing cognitive fatigue in single—task versus multitasking scenarios, our study offers a new method, which achieve a remarkable accuracy rate, thereby illuminating a new path in the research of cognitive fatigue.
Impact of intraoperative imaging on decision-making during spine surgery: a survey among spine surgeons using simulated intraoperative images
Authors: Bindels Bas J. J. , Hovenier Renée , Groot Olivier Q. , Vincken Koen L. , Rongen Jan J. , Smits Maarten L. J. , Verlaan Jorrit-Jan 
Published: March 2024

Abstract
Purpose
To assess whether the intention to intraoperatively reposition pedicle screws differs when spine surgeons evaluate the same screws with 2D imaging or 3D imaging.

Methods
In this online survey study, 21 spine surgeons evaluated eight pedicle screws from patients who had undergone posterior spinal fixation. In a simulated intraoperative setting, surgeons had to decide if they would reposition a marked pedicle screw based on its position in the provided radiologic imaging. The eight assessed pedicle screws varied in radiologic position, including two screws positioned within the pedicle, two breaching the pedicle cortex < 2 mm, two breaching the pedicle cortex 2–4 mm, and two positioned completely outside the pedicle. Surgeons assessed each pedicle screw twice without knowing and in random order: once with a scrollable three-dimensional (3D) image and once with two oblique fluoroscopic two-dimensional (2D) images.

Results
Almost all surgeons (19/21) intended to reposition more pedicle screws based on 3D imaging than on 2D imaging, with a mean number of pedicle screws to be repositioned of, respectively, 4.1 (± 1.3) and 2.0 (± 1.3; p < 0.001). Surgeons intended to reposition two screws placed completely outside the pedicle, one breaching 2-4mm, and one breaching < 2 mm more often based on 3D imaging.

Conclusion
When provided with 3D imaging, spine surgeons not only intend to intraoperatively reposition pedicle screws at risk of causing postoperative complications more often but also screws with acceptable positions. This study highlights the potential of intraoperative 3D imaging as well as the need for consensus on how to act on intraoperative 3D information.
Correlation between the MNCD classification-based staging of Parkinson’s disease and quality of life: a cross-sectional study
Authors: He Guixiang , Ren Jingru , Shi Haicun , Liu Weiguo , Lu Ming 
Published: March 2024

AbstractParkinson’s disease (PD) is a highly heterogeneous neurodegenerative disorder with varying clinical subtypes. Recently, a novel classification called MNCD (Motor/Non-motor/Cognition/Dependency) has been proposed, which can also include staging based on disease severity. We aim to investigate which staging, the MNCD classification and staging or Hoehn and Yahr (H&Y) staging, exhibits a stronger correlation with the 39-item Parkinson’s Disease Questionnaire (PDQ-39). In a cross-sectional study conducted at our single center, 357 PD patients were recruited. Data encompassed scores from various assessments such as the Movement Disorder Society of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Parts I, II, III and IV, Montreal Cognitive Assessment (MoCA), PDQ-39, and the H&Y scale. The mean age of these patients was 66.4 ± 9.1 years old, and the majority (54.6%) were male. MNCD stages: stage 1 (N = 3, 0.8%), stage 2 (N = 62, 17.4%), stage 3 (N = 187, 52.4%), stage 4 (N = 86, 24.1%), and stage 5 (N = 19, 5.3%). The top 5 most frequent PD-related clinical symptoms were sleep disturbances (89.6%), fatigue (69.7%), mild cognitive impairment (68.9%), constipation (65.8%), and postural instability (65.5%). The PDQ-39 demonstrated a positive correlation with both MNCD staging and H&Y staging. Moreover, the MNCD staging exhibited a stronger correlation with PDQ-39 compared to H&Y staging. The correlation between the MNCD classification and staging with the quality of life in PD patients is more statistically significant compared to the H&Y staging.
Diagnostic utility of ultrasound in pediatric nasal bone fractures: a systematic review and meta-analysis
Authors: Hassankhani Amir , Amoukhteh Melika , Jannatdoust Payam , Valizadeh Parya , Ghadimi Delaram J. , Saeedi Nikoo , Fathi Mobina , Yaghoobpoor Shirin , Adli Paniz , Vasavada Pauravi S. , Gholamrezanezhad Ali 
Published: March 2024

AbstractUltrasonography, a radiation-free and cost-effective modality, stands out as a promising tool for evaluating nasal bone fractures. Despite limited literature on its pediatric application, there is an increasing recognition of its potential to enhance diagnostic precision. To evaluate the diagnostic efficacy of ultrasound in detecting pediatric nasal bone fractures. Employing established guidelines, a systematic review and meta-analysis were conducted through a comprehensive literature search in PubMed, Scopus, Web of Science, and Embase databases until December 5, 2023. Inclusion criteria encompassed studies reporting diagnostic accuracy measures of ultrasound in pediatric patients with nasal bone fractures. Data extraction and analysis were undertaken for the selected studies. Involving four studies with 277 patients, ultrasound demonstrated a pooled sensitivity of 66.1% (95% CI: 35.1-87.5%) and specificity of 86.8% (95% CI: 80.1-91.4%) in diagnosing pediatric nasal fractures. The area under the receiver operating characteristic curve (AUC) was 0.88 (95% CI: 0.72–0.93). After excluding an outlier study, sensitivity and specificity increased to 78.0% (95% CI: 65.6-86.9%) and 87.8 (95% CI: 78.1-93.6%), respectively, with an AUC of 0.79 (95% CI: 0.75–0.94). Pooled positive and negative likelihood ratios were 5.11 (95% CI: 2.12–9.15) and 0.40 (95% CI: 0.14–0.77) before exclusion and 6.75 (95% CI: 3.47–12.30) and 0.26 (95% CI: 0.15–0.40) after exclusion of an outlier study, respectively. This study highlighted ultrasonography’s utility in diagnosing pediatric nasal bone fractures with high accuracy and specificity. However, caution is advised in relying solely on ultrasound due to suboptimal overall diagnostic performance, evident in likelihood ratios.
Cysteine- and glycine-rich protein 1 predicts prognosis and therapy response in patients with acute myeloid leukemia
Authors: Hao Qianqian , Liu Yu , Liu Yajun , Shi Luyao , Chen Yufei , Yang Lu , Jiang Zhongxing , Liu Yanfang , Wang Chong , Wang Shujuan , Sun Ling 
Published: March 2024

AbstractAcute myeloid leukemia (AML) is a heterogeneous disease with a poor prognosis. The current risk stratification system is essential but remains insufficient to select the best schedules. Cysteine-rich protein 1 (CSRP1) is a member of the CSRP family and associated with poor clinicopathological features in many tumors. This study aimed to explore the clinical significance and molecular mechanisms of cysteine- and glycine-rich protein 1 (CSRP1) in AML. RT-qPCR was used to detect the relative expression of CSRP1 in our clinical cohort. Functional enrichment analysis of CSRP1-related differentially expressed genes was carried out by GO/KEGG enrichment analysis, immune cell infiltration analysis, and protein–protein interaction (PPI) network. The OncoPredict algorithm was implemented to explore correlations between CSRP1 and drug resistance. CSRP1 was highly expressed in AML compared with normal samples. High CSRP1 expression was an independent poor prognostic factor. Functional enrichment analysis showed neutrophil activation and apoptosis were associated with CSRP1. In the PPI network, 19 genes were present in the most significant module, and 9 of them were correlated with AML prognosis. The high CSRP1 patients showed higher sensitivity to 5-fluorouracil, gemcitabine, rapamycin, cisplatin and lower sensitivity to fludarabine. CSRP1 may serve as a potential prognostic marker and a therapeutic target for AML in the future.
Expectations and Experiences Among Clinical Staff Regarding Implementation of Digital Pathology: A Qualitative Study at Two Departments of Pathology
Authors: Koefoed-Nielsen Helene , Kidholm Kristian , Frederiksen Marianne H. , Mikkelsen Minne L. N. 
Published: March 2024

AbstractThe aim of this study was to assess and evaluate the individual expectations and experiences regarding the implementation of digital pathology (DIPA) among clinical staff in two of the pathology departments in the Region of Southern Denmark before and during the implementation in their department. Seventeen semi-structured interviews based upon McKinsey 7-S framework were held both prior to and during implementation with both managers and employees at the two pathology departments. The interviewees were pathologists, medical doctors in internship in pathology (interns), biomedical laboratory scientists (BLS), secretaries, and a project lead. Using deductive and inductive coding resulted in five overall themes and appertaining sub-themes. The findings pointed to an overall positive attitude towards DIPA from the beginning. The clinical staff perceived being rewarded already during implementation with benefits such as improved collaboration both inter- and intra-departmentally promoting better acceptance of DIPA. The clinical staff also experienced some challenges, e.g., increase in turnaround times, which affected and concerned staff on a personal level. Especially BLS expressed experiencing a demanding and stressful transition due to unexpected increase in workload as well as some barriers for a potentially better implementation process. The key findings of this study were a need for better preparation of staff through transparent communication of the upcoming challenges of the transition to DIPA, more system-specific training beforehand, more allocation of time and resources in the implementation process, and more focus on BLS’ work tasks in the requirement specifications.