bluuebunny/crossref_metadata_2025_split huggingface dataset:
The educational paradigm shift—a phenomenographic study of medical teachers’ experiences of practices
Authors: Brauer Sanna , Kettunen Jaana , Levy Anna , Merenmies Jussi , Kulmala Petri 
Published: January 2023

Abstract
Background
This paper proposes a novel approach to the development of competence-oriented higher education, a national transformation aimed at harmonising and digitising undergraduate medical and dental education in Finland.

Methods
We apply phenomenography as a viable qualitative method for medical education research. To better understand medical teachers’ expectations towards the change in the educational paradigm, we need to study teachers’ experiences of the current practices in undergraduate medical and dental education. The phenomenographic approach facilitates solid links between research, educational development, and change.

Results
The phenomenographic study maps the qualitatively different ways in which medical teachers experience undergraduate medical and dental education practices. The answers reflect the changing educational paradigm in medical schools, suggesting practical implications for further development of medical and dental education and training. Core content analysis is preferred instructional scaffold for both teachers and students to prioritise the extensive medical education objectives. The change towards competence-based orientation is in progress and national co-operation accelerates its impact.

Conclusion
There is an obvious need to enrich the content of the current curriculum with national guidelines that aim for congruence in assessment and objectives. Our results suggest an assessment application for the theoretical concepts presented and promote the competence orientation of education throughout the curricula of medical and dental undergraduate education. Moreover, our results contribute to current European discourses on competence-based approaches in higher education. Up-to-date pedagogical faculty development programmes are a key prerequisite for teacher empowerment and future orientation in teaching and learning for healthcare professions.
Cross-cultural adaptation and validation of the Hospital Survey on Patient Safety Culture 2.0 – Brazilian version
Authors: Reis Claudia Tartaglia , Laguardia Josué , Bruno de Araújo Andreoli Paola , Nogueira Júnior Cassimiro , Martins Mônica 
Published: January 2023

Abstract
Background
Patient safety culture concerns the values, beliefs and standards shared by an organisation’s health staff and other personnel which influence their care provision actions and conduct. Several countries have made a priority of strengthening patient safety culture to improve the quality and safety of health care. In this direction, measuring the patient safety culture through validated instruments is a strategy applied worldwide. The purpose of this study was to adapt transculturally and validate the HSOPSC 2.0 to Brazilian Portuguese and the hospital context in Brazil.

Methods
Of the various validated scales for measuring safety culture, the instrument most used internationally is the Hospital Survey on Patient Safety Culture (HSOPSC) developed by the United States Agency for Healthcare Research and Quality in 2004 and revised in 2019, when version 2.0 was released. Adaptation was conducted on a universalist approach and the adapted instrument was then applied to a sample of 2,702 respondents (56% response rate) comprising staff of a large general hospital in the city of São Paulo. Construct validity was investigated by Exploratory Structural Equation Modelling-within-Confirmatory Factor Analysis (ESEM-within-CFA) and reliability was measured in each dimension by means of Cronbach alpha coefficients.

Results
ESEM fit indexes showed good data fit with the proposed model: χ2 = 634.425 df = 221 χ2/df ratio = 2.9 p-value < 0.0000; RMSEA = 0.045 (90% C.I. = 0.041—0.050) and probability RMSEA <  = .05 = 0.963; CFI = 0.986; TLI = 0.968. However, ten items had loads lower than 0.4. Cronbach alpha values were 0.6 or more for all dimensions, except Handoffs and information exchange ($$\alpha$$
α
= 0.50) and Staffing and work pace ($$\alpha$$
α
= 0.41).

Conclusion
The psychometric properties of the Brazilian version were found to be satisfactory, demonstrating good internal consistency and construct validity as expressed by estimates of reliability and indexes of model fit. However, given factor loadings smaller than 0.4 observed in ten items and considering that the scale translated and adapted to Portuguese was tested on a single sample during the Covid-19 pandemic, the authors recognize the need for it to be tested on other samples in Brazil to investigate its validity.
Antimicrobial activities of graphene oxide against biofilm and intracellular Staphylococcus aureus isolated from bovine mastitis
Authors: Saeed Shamsaldeen Ibrahim , Vivian Liang , Zalati C. W. Salma C. W. , Sani Nani Izreen Mohd , Aklilu Erkihun , Mohamad Maizan , Noor An’ Amt Mohamed , Muthoosamy Kasturi , Kamaruzzaman Nor Fadhilah 
Published: January 2023

Abstract
Background
S. aureus is one of the causative agents of bovine mastitis. The treatment using conventional antimicrobials has been hampered due to the development of antimicrobial resistance and the ability of the bacteria to form biofilms and localize inside the host cells.

Objectives
Here, the efficacy of graphene oxide (GO), a carbon-based nanomaterial, was tested against the biofilms and intracellular S. aureus invitro. Following that, the mechanism for the intracellular antimicrobial activities and GO toxicities was elucidated.

Methods
GO antibiofilm properties were evaluated based on the disruption of biofilm structure, and the intracellular antimicrobial activities were determined by the survival of S. aureus in infected bovine mammary cells following GO exposure. The mechanism for GO intracellular antimicrobial activities was investigated using endocytosis inhibitors. GO toxicity towards the host cells was assessed using a resazurin assay.

Results
At 100 ug/mL, GO reduced between 30 and 70% of S. aureus biofilm mass, suggesting GO’s ability to disrupt the biofilm structure. At 200 ug/mL, GO killed almost 80% of intracellular S. aureus, and the antimicrobial activities were inhibited when cells were pre-treated with cytochalasin D, suggesting GO intracellular antimicrobial activities were dependent on the actin-polymerization of the cell membrane. At < 250 ug/mL, GO enhanced the viability of the Mac-T cell, and cells were only affected at higher dosages.

Conclusion
The in vitro efficacy of GO against S. aureus in vitro suggested the compound could be further tested in Vivo to zrecognize its potential as one of the components of bovine mastitis therapy.
The diagnostic value of staging laparoscopy in gallbladder cancer: a nationwide cohort study
Authors: van Dooren Mike , de Savornin Lohman Elise A. J. , Brekelmans Eva , Vissers Pauline A. J. , Erdmann Joris I. , Braat Andries E. , Hagendoorn Jeroen , Daams Freek , van Dam Ronald M. , de Boer Marieke T. , van den Boezem Peter B. , Koerkamp Bas Groot , de Reuver Philip R. 
Published: January 2023

AbstractBackgroundDisseminated disease (DD) is often found at (re-)exploration in gallbladder cancer (GBC) patients. We aimed to assess the yield of staging laparoscopy (SL) and identify predictors for DD.MethodsThis retrospective study included patients from all Dutch academic centres with primary GBC (pGBC) and incidentally diagnosed GBC (iGBC) planned for (re-)resection. The yield of SL was determined. In iGBC, predictive factors for DD were assessed.ResultsIn total, 290 patients were included. Of 183 included pGBC patients, 143 underwent laparotomy without SL, and 42 (29%) showed DD perioperatively. SL, conducted in 40 patients, identified DD in eight. DD was found in nine of 32 patients who underwent laparotomy after SL.Of 107 included iGBC patients, 100 underwent laparotomy without SL, and 19 showed DD perioperatively. SL, conducted in seven patients, identified DD in one. Cholecystitis (OR= 4.25; 95%CI1.51–11.91) and primary R1/R2 resection (OR= 3.94; 95%CI1.39–11.19) were independent predictive factors for DD.ConclusionsIn pGBC patients, SL may identify DD in up to 20% of patients and should be part of standard management. In iGBC patients, SL is indicated after primary resection for cholecystitis and after initial R1/R2 resection due to the association of these factors with DD.
Identification of key pharmacological components and targets for Aidi injection in the treatment of pancreatic cancer by UPLC-MS, network pharmacology, and in vivo experiments
Authors: Wang Haojia , Wu Zhishan , Fan Xiaotian , Wu Chao , Lu Shan , Geng Libo , Stalin Antony , Zhu Yingli , Zhang Fanqin , Huang Jiaqi , Liu Pengyun , Li Huiying , You Leiming , Wu Jiarui 
Published: January 2023

Abstract
Background
Pancreatic cancer is one of the most lethal cancers worldwide. Aidi injection (ADI) is a representative antitumor medication based on Chinese herbal injection, but its antitumor mechanisms are still poorly understood.

Materials and methods
In this work, the subcutaneous xenograft model of human pancreatic cancer cell line Panc-1 was established in nude mice to investigate the anticancer effect of ADI in vivo. We then determined the components of ADI using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS) and explored the possible molecular mechanisms against pancreatic cancer using network pharmacology.

Results
In vivo experiments, the volume, weight, and degree of histological abnormalities of implanted tumors were significantly lower in the medium and high concentration ADI injection groups than in the control group. Network pharmacology analysis identified four active components of ADI and seven key targets, TNF, VEGFA, HSP90AA1, MAPK14, CASP3, P53 and JUN. Molecular docking also revealed high affinity between the active components and the target proteins, including Astragaloside IV to P53 and VEGFA, Ginsenoside Rb1 to CASP3 and Formononetin to JUN.

Conclusion
ADI could reduce the growth rate of tumor tissue and alleviate the structural abnormalities in tumor tissue. ADI is predicted to act on VEGFA, P53, CASP3, and JUN in ADI-mediated treatment of pancreatic cancer.
Neurophysiological assessment of cortical activity in DEPDC5- and NPRL3-related epileptic mTORopathies
Authors: Mabika Madora , Agbogba Kristian , Côté Samantha , Lippé Sarah , Riou Émilie , Cieuta Cécile , Lepage Jean-François 
Published: January 2023

Abstract
Background
Mutations in the GATOR1 complex genes, DEPDC5 and NPRL3, play a major role in the development of lesional and non-lesional focal epilepsy through increased mTORC1 signalling. We aimed to assess the effects of mTORC1 hyperactivation on GABAergic inhibitory circuits, in 3 and 5 individuals carrying DEPDC5 and NPRL3 mutations respectively using a multimodal approach including transcranial magnetic stimulation (TMS), magnetic resonance spectroscopy (MRS), and electroencephalography (EEG).

Results
Inhibitory functions probed by TMS and MRS showed no effect of mutations on cortical GABAergic receptor-mediated inhibition and GABA concentration, in both cortical and subcortical regions. However, stronger EEG theta oscillations and stronger and more synchronous gamma oscillations were observed in DEPDC5 and NPRL3 mutations carriers.

Conclusions
These results suggest that DEPDC5 and NPRL3-related epileptic mTORopathies may not directly modulate GABAergic functions but are nonetheless characterized by a stronger neural entrainment that may be reflective of a cortical hyperexcitability mediated by increased mTORC1 signaling.
Repurposing nitric oxide donating drugs in cancer therapy through immune modulation
Authors: Li Chung-Yen , Anuraga Gangga , Chang Chih-Peng , Weng Tzu-Yang , Hsu Hui-Ping , Ta Hoang Dang Khoa , Su Pei-Fang , Chiu Pin-Hsuan , Yang Shiang-Jie , Chen Feng-Wei , Ye Pei-Hsuan , Wang Chih-Yang , Lai Ming-Derg 
Published: January 2023

Abstract
Background
Nitric oxide-releasing drugs are used for cardiovascular diseases; however, their effects on the tumor immune microenvironment are less clear. Therefore, this study explored the impact of nitric oxide donors on tumor progression in immune-competent mice.

Methods
The effects of three different nitric oxide-releasing compounds (SNAP, SNP, and ISMN) on tumor growth were studied in tumor-bearing mouse models. Three mouse tumor models were used: B16F1 melanoma and LL2 lung carcinoma in C57BL/6 mice, CT26 colon cancer in BALB/c mice, and LL2 lung carcinoma in NOD/SCID mice. After nitric oxide treatment, splenic cytokines and lymphocytes were analyzed by cytokine array and flow cytometry, and tumor-infiltrating lymphocytes in the TME were analyzed using flow cytometry and single-cell RNA sequencing.

Results
Low doses of three exogenous nitric oxide donors inhibited tumor growth in two immunocompetent mouse models but not in NOD/SCID immunodeficient mice. Low-dose nitric oxide donors increase the levels of splenic cytokines IFN-γ and TNF-α but decrease the levels of cytokines IL-6 and IL-10, suggesting an alteration in Th2 cells. Nitric oxide donors increased the number of CD8+ T cells with activation gene signatures, as indicated by single-cell RNA sequencing. Flow cytometry analysis confirmed an increase in infiltrating CD8+ T cells and dendritic cells. The antitumor effect of nitric oxide donors was abolished by depletion of CD8+ T cells, indicating the requirement for CD8+ T cells. Tumor inhibition correlated with a decrease in a subtype of protumor macrophages and an increase in a subset of Arg1-positive macrophages expressing antitumor gene signatures. The increase in this subset of macrophages was confirmed by flow cytometry analysis. Finally, the combination of low-dose nitric oxide donor and cisplatin induced an additive cancer therapeutic effect in two immunocompetent animal models. The enhanced therapeutic effect was accompanied by an increase in the cells expressing the gene signature of NK cell.

Conclusions
Low concentrations of exogenous nitric oxide donors inhibit tumor growth in vivo by regulating T cells and macrophages. CD8+ T cells are essential for antitumor effects. In addition, low-dose nitric oxide donors may be combined with chemotherapeutic drugs in cancer therapy in the future.
Blood parasites (Trypanosoma, Leucocytozoon, Haemoproteus) in the Eurasian sparrowhawk (Accipiter nisus): diversity, incidence and persistence of infection at the individual level
Authors: Svobodová Milena , Čepička Ivan , Zídková Lenka , Kassahun Aysheshm , Votýpka Jan , Peške Lubomír , Hrazdilová Kristýna , Brzoňová Jana , Voříšek Petr , Weidinger Karel 
Published: January 2023

Abstract
Background
A high prevalence of parasites may result from life-long persistence of infection or from high reinfection rates. We have studied blood parasites in a breeding population of the accipitrid raptor, Eurasian sparrowhawk (Accipiter nisus), to determine parasite diversity and turnover.

Methods
During this 7-year study, 210 adult Eurasian sparrowhawks breeding in the city of Prague were checked for parasites using several diagnostic methods.

Results
In both female and male raptors, parasites of the genus Leucocytozoon were the most prevalent (92% and 85%, respectively) followed in decreasing order of prevalence by those of genus Trypanosoma (74% and 68%, respectively) and genus Haemoproteus (46% and 16%, respectively). The prevalence of all parasites increased with age in both sexes, with the females at each respective age having the higher prevalence. There was a positive association between Haemoproteus and Leucocytozoon infections. Persistence at the individual level was higher than incidence for Trypanosoma and Haemoproteus. In the case of Leucocytozoon and Trypanosoma, most individuals probably become infected in their first year of life or even before dispersal from the nest. The detected parasites belonged to Trypanosoma avium sensu stricto, Leucocytozoon sp. (haplotypes ACNI1 and ACNI3) and Leucocytozoon mathisi (haplotype ACNI4) and two new lineages of the Haemoproteus elani complex (ACCNIS6 and ACCNIS7). Detailed analysis of parasite lineages in individuals that were repeatedly sampled revealed lineage turnover that would otherwise remain hidden. Phylogenetic analysis revealed that the detected Haemoproteus belongs to a phylogenetically distant group whose taxonomic position requires further analysis.

Conclusions
All three genera of blood parasites persist in infected individuals, thus enabling sustainability of vector transmission cycles. Prevalence increases with age; however, there is a high turnover of Leucocytozoon lineages. No clear evidence of parasite-induced mortality was found, and most of the individuals were infected early in life, particularly in the case of Leucocytozoon.

Graphical abstract
A novel human tau knock-in mouse model reveals interaction of Abeta and human tau under progressing cerebral amyloidosis in 5xFAD mice
Authors: Barendrecht Susan , Schreurs An , Geissler Stefanie , Sabanov Victor , Ilse Victoria , Rieckmann Vera , Eichentopf Rico , Künemund Anja , Hietel Benjamin , Wussow Sebastian , Hoffmann Katrin , Körber-Ferl Kerstin , Pandey Ravi , Carter Gregory W. , Demuth Hans-Ulrich , Holzer Max , Roßner Steffen , Schilling Stephan , Preuss Christoph , Balschun Detlef , Cynis Holger 
Published: January 2023

Abstract
Background
Hyperphosphorylation and intraneuronal aggregation of the microtubule-associated protein tau is a major pathological hallmark of Alzheimer’s disease (AD) brain. Of special interest is the effect of cerebral amyloid beta deposition, the second main hallmark of AD, on human tau pathology. Therefore, studying the influence of cerebral amyloidosis on human tau in a novel human tau knock-in (htau-KI) mouse model could help to reveal new details on their interplay.

Methods
We studied the effects of a novel human htau-KI under fast-progressing amyloidosis in 5xFAD mice in terms of correlation of gene expression data with human brain regions, development of Alzheimer’s-like pathology, synaptic transmission, and behavior.

Results
The main findings are an interaction of human beta-amyloid and human tau in crossbred 5xFADxhtau-KI observed at transcriptional level and corroborated by electrophysiology and histopathology. The comparison of gene expression data of the 5xFADxhtau-KI mouse model to 5xFAD, control mice and to human AD patients revealed conspicuous changes in pathways related to mitochondria biology, extracellular matrix, and immune function. These changes were accompanied by plaque-associated MC1-positive pathological tau that required the htau-KI background. LTP deficits were noted in 5xFAD and htau-KI mice in contrast to signs of rescue in 5xFADxhtau-KI mice. Increased frequencies of miniature EPSCs and miniature IPSCs indicated an upregulated presynaptic function in 5xFADxhtau-KI.

Conclusion
In summary, the multiple interactions observed between knocked-in human tau and the 5xFAD-driven progressing amyloidosis have important implications for future model development in AD.
Critical assessment of synthetic accessibility scores in computer-assisted synthesis planning
Authors: Skoraczyński Grzegorz , Kitlas Mateusz , Miasojedow Błażej , Gambin Anna 
Published: January 2023

AbstractModern computer-assisted synthesis planning tools provide strong support for this problem. However, they are still limited by computational complexity. This limitation may be overcome by scoring the synthetic accessibility as a pre-retrosynthesis heuristic. A wide range of machine learning scoring approaches is available, however, their applicability and correctness were studied to a limited extent. Moreover, there is a lack of critical assessment of synthetic accessibility scores with common test conditions.In the present work, we assess if synthetic accessibility scores can reliably predict the outcomes of retrosynthesis planning. Using a specially prepared compounds database, we examine the outcomes of the retrosynthetic tool . We test whether synthetic accessibility scores: SAscore, SYBA, SCScore, and RAscore accurately predict the results of retrosynthesis planning. Furthermore, we investigate if synthetic accessibility scores can speed up retrosynthesis planning by better prioritizing explored partial synthetic routes and thus reducing the size of the search space. For that purpose, we analyze the partial solutions search trees, their structure, and complexity parameters, such as the number of nodes, or treewidth.We confirm that synthetic accessibility scores in most cases well discriminate feasible molecules from infeasible ones and can be potential boosters of retrosynthesis planning tools. Moreover, we show the current challenges of designing computer-assisted synthesis planning tools. We conclude that hybrid machine learning and human intuition-based synthetic accessibility scores can efficiently boost the effectiveness of computer-assisted retrosynthesis planning, however, they need to be carefully crafted for retrosynthesis planning algorithms.The source code of this work is publicly available at https://github.com/grzsko/ASAP.
Robust and accurate performance anomaly detection and prediction for cloud applications: a novel ensemble learning-based framework
Authors: Xin Ruyue , Liu Hongyun , Chen Peng , Zhao Zhiming 
Published: January 2023

AbstractEffectively detecting run-time performance anomalies is crucial for clouds to identify abnormal performance behavior and forestall future incidents. To be used for real-world applications, an effective anomaly detection framework should meet three main challenging requirements: high accuracy for identifying anomalies, good robustness when application patterns change, and prediction ability for upcoming anomalies. Unfortunately, existing research about performance anomaly detection usually focuses on improving detection accuracy, while little research tackles the three challenges simultaneously. We conduct experiments for existing detection methods on multiple application monitoring data, and results show that existing detection methods usually focus on different features in data, which will lead to their diverse performance on different data patterns. Therefore, existing anomaly detection methods have difficulty improving detection accuracy and robustness and predicting anomalies. To address the three requirements, we propose an Ensemble Learning-Based Detection (ELBD) framework which integrates existing well-selected detection methods. The framework includes three classic linear ensemble methods (maximum, average, and weighted average) and a novel deep ensemble method. Our experiments show that the ELBD framework realizes better detection accuracy and robustness, where the deep ensemble method can achieve the most accurate and robust detection for cloud applications. In addition, it can predict anomalies in the next four minutes with an F1 score higher than 0.8. The paper also proposes a new indicator $$ARP\_score$$

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to measure detection accuracy, robustness, and multi-step prediction ability. The $$ARP\_score$$

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P
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of the deep ensemble method is 5.1821, which is much higher than other detection methods.