bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparing extraction method efficiency for high-throughput palaeoproteomic bone species identification
Authors: Mylopotamitaki Dorothea , Harking Florian S. , Taurozzi Alberto J. , Fagernäs Zandra , Godinho Ricardo M. , Smith Geoff M. , Weiss Marcel , Schüler Tim , McPherron Shannon P. , Meller Harald , Cascalheira João , Bicho Nuno , Olsen Jesper V. , Hublin Jean-Jacques , Welker Frido 
Published: October 2023

AbstractHigh-throughput proteomic analysis of archaeological skeletal remains provides information about past fauna community compositions and species dispersals in time and space. Archaeological skeletal remains are a finite resource, however, and therefore it becomes relevant to optimize methods of skeletal proteome extraction. Ancient proteins in bone specimens can be highly degraded and consequently, extraction methods for well-preserved or modern bone might be unsuitable for the processing of highly degraded skeletal proteomes. In this study, we compared six proteomic extraction methods on Late Pleistocene remains with variable levels of proteome preservation. We tested the accuracy of species identification, protein sequence coverage, deamidation, and the number of post-translational modifications per method. We find striking differences in obtained proteome complexity and sequence coverage, highlighting that simple acid-insoluble proteome extraction methods perform better in highly degraded contexts. For well-preserved specimens, the approach using EDTA demineralization and protease-mix proteolysis yielded a higher number of identified peptides. The protocols presented here allowed protein extraction from ancient bone with a minimum number of working steps and equipment and yielded protein extracts within three working days. We expect further development along this route to benefit large-scale screening applications of relevance to archaeological and human evolution research.
Pan-cancer analysis revealing that PTPN2 is an indicator of risk stratification for acute myeloid leukemia
Authors: Wang Xuanyu , Wu Sanyun , Sun Le , Jin Peipei , Zhang Jianmin , Liu Wen , Zhan Zhuo , Wang Zisong , Liu Xiaoping , He Li 
Published: October 2023

AbstractThe non-receptor protein tyrosine phosphatases gene family (PTPNs) is involved in the tumorigenesis and development of many cancers, but the role of PTPNs in acute myeloid leukemia (AML) remains unclear. After a comprehensive evaluation on the expression patterns and immunological effects of PTPNs using a pan-cancer analysis based on RNA sequencing data obtained from The Cancer Genome Atlas, the most valuable gene PTPN2 was discovered. Further investigation of the expression patterns of PTPN2 in different tissues and cells showed a robust correlation with AML. PTPN2 was then systematically correlated with immunological signatures in the AML tumor microenvironment and its differential expression was verified using clinical samples. In addition, a prediction model, being validated and compared with other models, was developed in our research. The systematic analysis of PTPN family reveals that the effect of PTPNs on cancer may be correlated to mediating cell cycle-related pathways. It was then found that PTPN2 was highly expressed in hematologic diseases and bone marrow tissues, and its differential expression in AML patients and normal humans was verified by clinical samples. Based on its correlation with immune infiltrates, immunomodulators, and immune checkpoint, PTPN2 was found to be a reliable biomarker in the immunotherapy cohort and a prognostic predictor of AML. And PTPN2'riskscore can accurately predict the prognosis and response of cancer immunotherapy. These findings revealed the correlation between PTPNs and immunophenotype, which may be related to cell cycle. PTPN2 was differentially expressed between clinical AML patients and normal people. It is a diagnostic biomarker and potentially therapeutic target, providing targeted guidance for clinical treatment.
Excitatory purinergic and cholinergic expression changed in a partial bladder outlet obstruction-induced overactive bladder rat model
Authors: Huang Jingyi , Li Hongliang , Zhang Yao , Liu Jiaye , Cao Hongying , Long Yongling 
Published: October 2023

AbstractOveractive bladder (OAB) is a common, long-term symptom complex with a high prevalence in women worldwide. OAB has caused a social burden, and effective treatments are urgently needed. However, the pathogenesis of OAB has yet to be elucidated. Model rats underwent bladder outlet obstruction surgery. In the 2nd, 3rd, and 4th weeks after surgery, metabolic cages were used to detect the 12 h urine volume of rats in the sham and model groups. The urodynamic parameters bladder leak point pressure (BPLL), maximum voiding pressure (MVP), residual volume (RV), maximum bladder capacity (MBC), bladder compliance (BC), voided efficiency (VE), and non-voiding contractions (NVCs) were also detected. Moreover, the contractile responses of isolated detrusor muscles to electrical and carbachol stimulation were examined at the abovementioned time points. At the 4th week after surgery, the bladders of both groups were obtained for hematoxylin–eosin (H&E) and Masson’s trichrome staining. Real-time qPCR and Western blot were performed to quantify the expression of choline acetyltransferase (ChAT) and solute carrier family 17 member 9 (SLC17A9). At week 4, compared with the sham group, the 12 h urine volume of PBOO group increased significantly. The BLPP, MVP, VE, MBC, and NVCs increased significantly, and the VE was significantly reduced in 4-week PBOO group. The contractile responses of isolated detrusor muscles to electrical and carbachol stimulation significantly increased in 4-week PBOO group. In the 4-week PBOO group, the bladder wall and the ratio of bladder muscle to collagen within the bladder smooth muscle layer wall were significantly higher than those in the sham group. ChAT and SLC17A9 mRNA and protein expression in the OAB model rats significantly increased. At 4 weeks after PBOO, the OAB model was successfully established. The gene and protein expression levels of ChAT and SLC17A9 increased in the bladder of the OAB model, suggesting that OAB may be related to increased excitatory purinergic and cholinergic expression.
Comparison between an SGLT2 inhibitor and insulin in tumor-to-tissue contrasts in 18F-FDG PET imaging of diabetic mice
Authors: Meidai Liang , Yujing Du , Zhaoyu Liu , Shanshi Li , Guangyu Zhao , Yan Fan , Xiuying Yang , Jianhua Zhang 
Published: October 2023

Abstract18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) has been widely utilized for tumor diagnosis. Hyperglycemia affects the 18F-FDG uptake and reduces tumor-to-tissue contrasts, however, ideal hypoglycemic drugs are lacking. This study compared the role of insulin with the novel widely used hypoglycemic drug, sodium-glucose cotransporter 2 (SGLT2) inhibitor, on 18F-FDG PET imaging in diabetic conditions. The streptozotocin (STZ)-induced diabetic C57BL/6N mice were inoculated with B16 (mouse melanoma) cells to establish the xenograft tumor model. After the mice had been administrated with dapagliflozin (30 mg/kg, IG) or insulin (0.75 U/kg, IP) for one hour, 9.25 MBq/10 g 18F-FDG was injected. Biodistributions were detected by gamma counting and microPET imaging. The results showed dapagliflozin did not significantly affect the 18F-FDG uptake in tumors but reduced uptake in reference tissues, resulting in a significant increase in the tumor-to-skeletal muscle ratio. Conversely, insulin increased 18F-FDG uptake in tumors without significant reduction in uptake in reference tissues; Although there was an observable improvement in tumor imaging, it did not reach significantly statistical differences. This study suggests that insulin and SGLT2 inhibitor yield comparable effects on the quality of 18F-FDG PET imaging in diabetic patients. Nevertheless, SGLT2 inhibitors would be more suitable when skeletal muscle is used as reference tissue.
Comparative analysis between 2D and 3D colorectal cancer culture models for insights into cellular morphological and transcriptomic variations
Authors: Abbas Zaid Nsaif , Al-Saffar Ali Z. , Jasim Saba Mahdi , Sulaiman Ghassan M. 
Published: October 2023

AbstractDrug development is a time-consuming and expensive process, given the low success rate of clinical trials. Now, anticancer drug developments have shifted to three-dimensional (3D) models which are more likely to mimic tumor behavior compared to traditional two-dimensional (2D) cultures. A comparative study among different aspects was conducted between 2D and 3D cultures using colorectal cancer (CRC) cell lines, in addition, Formalin-Fixed Paraffin-Embedded (FFPE) block samples of patients with CRC were used for evaluation. Compared to the 2D culture, cells grown in 3D displayed significant (p < 0.01) differences in the pattern of cell proliferation over time, cell death phase profile, expression of tumorgenicity-related genes, and responsiveness to 5-fluorouracil, cisplatin, and doxorubicin. Epigenetically, 3D cultures and FFPE shared the same methylation pattern and microRNA expression, while 2D cells showed elevation in methylation rate and altered microRNA expression. Lastly, transcriptomic study depending on RNA sequencing and thorough bioinformatic analyses showed significant (p-adj < 0.05) dissimilarity in gene expression profile between 2D and 3D cultures involving thousands of genes (up/down-regulated) of multiple pathways for each cell line. Taken together, the study provides insights into variations in cellular morphologies between cells cultured in 2D and 3D models.
A text mining approach to categorize patient safety event reports by medication error type
Authors: Boxley Christian , Fujimoto Mari , Ratwani Raj M. , Fong Allan 
Published: October 2023

AbstractPatient safety reporting systems give healthcare provider staff the ability to report medication related safety events and errors; however, many of these reports go unanalyzed and safety hazards go undetected. The objective of this study is to examine whether natural language processing can be used to better categorize medication related patient safety event reports. 3,861 medication related patient safety event reports that were previously annotated using a consolidated medication error taxonomy were used to develop three models using the following algorithms: (1) logistic regression, (2) elastic net, and (3) XGBoost. After development, models were tested, and model performance was analyzed. We found the XGBoost model performed best across all medication error categories. ‘Wrong Drug’, ‘Wrong Dosage Form or Technique or Route’, and ‘Improper Dose/Dose Omission’ categories performed best across the three models. In addition, we identified five words most closely associated with each medication error category and which medication error categories were most likely to co-occur. Machine learning techniques offer a semi-automated method for identifying specific medication error types from the free text of patient safety event reports. These algorithms have the potential to improve the categorization of medication related patient safety event reports which may lead to better identification of important medication safety patterns and trends.
A quantitative method for determination of colistin E2 methanesulphonate in human plasma by 15N-labeled colistin E2
Authors: Xu Hongjiang , Li Yanan , Zhang Jing , Zhang Jinhua , Lu Jianguang , Zhang Xiquan , Yang Ling , Zhao Wenjie , Feng Jun 
Published: October 2023

AbstractThe single-component colistin E2, with superior antibacterial activity and lower toxicity, was being developed as the latest generation of polymyxin drugs. However, colistin E2 has not been tested quantitatively in biological matrices. In this study, based on the quantitative detection of colistin methanesulphonate (CMS) and colistin by Zhao et al., 15N-labeled colistin E2 was used as an internal standard (IS) for a more accurate quantitative detection of CMS E2 in human plasma. A rapid ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC–MS/MS) assay method was developed for determination of CMS E2 and colistin E2 in human plasma. After pretreatment of plasma samples by 96-well SPE Supra-Clean Weak Cation Exchange (WCX) plate, the formed colistin E2 was detected and quantified by UHPLC–MS/MS system. All plasma lots were found to be free of interferences with the analyte. The matrix has no effect on the quantitation of the analyte. No significant effect of the carryover was observed. The dilution integrity was demonstrated in plasma samples without the loss of accuracy and precision. The lower limit of quantification (LLOQ) was 0.0300 mg/L for colistin E2 in plasma with accuracy (relative error, 5.1–12.7%) and precision (relative standard deviation,  − 5.7–9.3%). Stability of CMS E2 and colistin E2 was demonstrated in biological samples before and during sample treatment, and in the extract. Furthermore, this method was successfully applied to the analysis of plasma samples obtained from Chinese healthy volunteers receiving a single intravenous CMS E2 dose of 5 mg/kg. In conclusion, the detection method was characterized by speed and high accuracy, which laid a solid foundation for the subsequent development of CMS E2 drug.
A pill as a quick solution: association between painkiller intake, empathy, and prosocial behavior
Authors: Banwinkler Magdalena , Rütgen Markus , Lamm Claus , Hartmann Helena 
Published: October 2023

AbstractPrevious research has demonstrated a link between the administration of analgesic drugs and the reduction of empathy levels in humans. This apparent blunting effect of pain medication has been explained through shared neural mechanisms for the first-hand and the empathic experience of pain (simulation theory). Considering that analgesics are among the most consumed drugs in the world and the ability to empathize with others is fundamental to human social interactions, the aim of the present study was to investigate whether the typical day-to-day analgesic consumption rate in Austria and Germany is associated with a reduction in empathy and prosocial behavior. We therefore collected self-reports of analgesic consumption behavior as well as empathy for pain and prosocial behavior measures in an online survey (n = 940). Analyses revealed no significant association between the analgesic intake frequency and measures of empathy or prosocial behavior. However, liberal intake of analgesics (i.e. mind-set of “a pill is a quick solution”) was linked to lower empathic concern and helping behavior, which may hint towards a negative effect in people who take pain medication for non-pain related issues or episodes of low pain. Nevertheless, further research is needed to investigate the effects of analgesic drugs in high frequency users.
Computational completion of the Aurora interaction region of N-Myc in the Aurora a kinase complex
Authors: Altiner Pinar , Çınaroğlu Süleyman Selim , Timucin Ahmet Can , Timucin Emel 
Published: October 2023

AbstractInhibiting protein–protein interactions of the Myc family is a viable pharmacological strategy for modulation of the levels of Myc oncoproteins in cancer. Aurora A kinase (AurA) and N-Myc interaction is one of the most attractive targets of this strategy because formation of this complex blocks proteasomal degradation of N-Myc in neuroblastoma. Two crystallization studies have captured this complex (PDB IDs: 5g1x, 7ztl), partially resolving the AurA interaction region (AIR) of N-Myc. Prompted by the missing N-Myc fragment in these crystal structures, we modeled the complete structure between AurA and N-Myc, and comprehensively analyzed how the incomplete and complete N-Myc behave in complex by molecular dynamics simulations. Molecular dynamics simulations of the incomplete PDB complex (5g1x) repeatedly showed partial dissociation of the short N-Myc fragment (61–89) from the kinase. The missing N-Myc (19–60) fragment was modeled utilizing the N-terminal lobe of AurA as the protein–protein interaction surface, wherein TPX2, a well-known partner of AurA, also binds. Binding free energy calculations along with flexibility analysis confirmed that the complete AIR of N-Myc stabilizes the complex, accentuating the N-terminal lobe of AurA as a binding site for the missing N-Myc fragment (19–60). We further generated additional models consisting of only the missing N-Myc (19–60), and the fused form of TPX2 (7–43) and N-Myc (61–89). These partners also formed more stable interactions with the N-terminal lobe of AurA than did the incomplete N-Myc fragment (61–89) in the 5g1x complex. Altogether, this study provides structural insights into the involvement of the N-terminus of the AIR of N-Myc and the N-terminal lobe of AurA in formation of a stable complex, reflecting its potential for effective targeting of N-Myc.
Identification of PCB congeners and their thresholds associated with diabetes using decision tree analysis
Authors: Lan Tuo , Liu Buyun , Bao Wei , Thorne Peter S. 
Published: October 2023

AbstractFew studies have investigated the potential combined effects of multiple PCB congeners on diabetes. To address this gap, we used data from 1244 adults in the National Health and Nutrition Examination Survey (NHANES) 2003–2004. We used (1) classification trees to identify serum PCB congeners and their thresholds associated with diabetes; and (2) logistic regression to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of diabetes with combined PCB congeners. Of the 40 PCB congeners examined, PCB 126 has the strongest association with diabetes. The adjusted OR of diabetes comparing PCB 126 > 0.025 to ≤ 0.025 ng/g was 2.14 (95% CI 1.30–3.53). In the subpopulation with PCB 126 > 0.025 ng/g, a lower PCB 101 concentration was associated with an increased risk of diabetes (comparing PCB 101 < 0.72 to ≥ 0.72 ng/g, OR 3.3, 95% CI 1.27–8.55). In the subpopulation with PCB 126 > 0.025 & PCB 101 < 0.72 ng/g, a higher PCB 49 concentration was associated with an increased risk of diabetes (comparing PCB 49 > 0.65 to ≤ 0.65 ng/g, OR 2.79, 95% CI 1.06–7.35). This nationally representative study provided new insights into the combined associations of PCBs with diabetes.
Videoconference fatigue from a neurophysiological perspective: experimental evidence based on electroencephalography (EEG) and electrocardiography (ECG)
Authors: Riedl René , Kostoglou Kyriaki , Wriessnegger Selina C. , Müller-Putz Gernot R. 
Published: October 2023

AbstractIn the recent past, many organizations and people have substituted face-to-face meetings with videoconferences. Among others, tools like Zoom, Teams, and Webex have become the “new normal” of human social interaction in many domains (e.g., business, education). However, this radical adoption and extensive use of videoconferencing tools also has a dark side, referred to as videoconference fatigue (VCF). To date only self-report evidence has shown that VCF is a serious issue. However, based on self-reports alone it is hardly possible to provide a comprehensive understanding of a cognitive phenomenon like VCF. Against this background, we examined VCF also from a neurophysiological perspective. Specifically, we collected and analyzed electroencephalography (continuous and event-related) and electrocardiography (heart rate and heart rate variability) data to investigate whether VCF can also be proven on a neurophysiological level. We conducted a laboratory experiment based on a within-subjects design (N = 35). The study context was a university lecture, which was given in a face-to-face and videoconferencing format. In essence, the neurophysiological data—together with questionnaire data that we also collected—show that 50 min videoconferencing, if compared to a face-to-face condition, results in changes in the human nervous system which, based on existing literature, can undoubtedly be interpreted as fatigue. Thus, individuals and organizations must not ignore the fatigue potential of videoconferencing. A major implication of our study is that videoconferencing should be considered as a possible complement to face-to-face interaction, but not as a substitute.
Validation and evaluation of subject-specific finite element models of the pediatric knee
Authors: Karimi Dastgerdi Ayda , Esrafilian Amir , Carty Christopher P. , Nasseri Azadeh , Yahyaiee Bavil Alireza , Barzan Martina , Korhonen Rami K. , Astori Ivan , Hall Wayne , Saxby David John 
Published: October 2023

AbstractFinite element (FE) models have been widely used to investigate knee joint biomechanics. Most of these models have been developed to study adult knees, neglecting pediatric populations. In this study, an atlas-based approach was employed to develop subject-specific FE models of the knee for eight typically developing pediatric individuals. Initially, validation simulations were performed at four passive tibiofemoral joint (TFJ) flexion angles, and the resulting TFJ and patellofemoral joint (PFJ) kinematics were compared to corresponding patient-matched measurements derived from magnetic resonance imaging (MRI). A neuromusculoskeletal-(NMSK)-FE pipeline was then used to simulate knee biomechanics during stance phase of walking gait for each participant to evaluate model simulation of a common motor task. Validation simulations demonstrated minimal error and strong correlations between FE-predicted and MRI-measured TFJ and PFJ kinematics (ensemble average of root mean square errors < 5 mm for translations and < 4.1° for rotations). The FE-predicted kinematics were strongly correlated with published reports (ensemble average of Pearson's correlation coefficients (ρ) > 0.9 for translations and ρ > 0.8 for rotations), except for TFJ mediolateral translation and abduction/adduction rotation. For walking gait, NMSK-FE model-predicted knee kinematics, contact areas, and contact pressures were consistent with experimental reports from literature. The strong agreement between model predictions and experimental reports underscores the capability of sequentially linked NMSK-FE models to accurately predict pediatric knee kinematics, as well as complex contact pressure distributions across the TFJ articulations. These models hold promise as effective tools for parametric analyses, population-based clinical studies, and enhancing our understanding of various pediatric knee injury mechanisms. They also support intervention design and prediction of surgical outcomes in pediatric populations.