bluuebunny/crossref_metadata_2025_split huggingface dataset:
All-digital training course in neurophysiology: lessons learned from the COVID-19 pandemic
Authors: Duszenko Michael , Fröhlich Nicole , Kaupp Ariane , Garaschuk Olga 
Published: January 2022

AbstractBackgroundThe social distancing and suspension of on-campus learning, imposed by the COVID-19 pandemic, are likely to influence medical training for months if not years. Thus, there is a need for digital replacement for classroom teaching, especially for hands-on courses, during which social distancing is hardly possible. Here, we investigated students’ learning experience with a newly designed digital training course in neurophysiology, with intercalated teaching blocks in either asynchronous (unsupervised online lectures and e-labs) or synchronous (online seminars, supervised by instructors) formats.MethodsThe accompanying anonymized prospective study included 146 student participants. At the beginning and the end of the course, students were invited to answer anonymous online questionnaires with 18 and 25 items, respectively. We conducted both qualitative analyses of students’ survey responses and statistical analyses of the results of cohort-specific summative examinations. The summative assessment results were compared both between 4 current cohorts and with the respective historical cohorts.ResultsDespite having little prior experience with e-learning (4.5 on the 1-7 scale), students adapted remarkably well to this online format. They appreciated its higher flexibility, time efficiency, student-oriented nature (especially when using inverted classroom settings), tolerance towards the individual learning style and family circumstances, and valued the ability to work through lectures and e-labs at their own learning speed. The major complaints concerned diminished social contacts with instructors and fellow students, the inability to ask questions as they occur, and the lack of sufficient technical expertise. The students valued the newly developed e-labs, especially the implementation of interactive preparative measures (PreLabs) and the intuitive lab design offered by the chosen software (Lt Platformfrom AD Instruments). The summative examinations at the end of the course documented the quality of knowledge transfer, which was comparable to that of previous classically instructed cohorts.ConclusionDespite the missing personal contact between the faculty and the students, inherent to online teaching, the all-digital training course described here proofed to be of good educational value and, in case the pandemic continues, is worse considering for the future. Some of the described building blocks, like digital lectures or interactive PreLabs, may survive the pandemics to enrich the medical education toolbox in the future.
Using communities of practice as a lens for exploring experiential pharmacy learning in general practice: Are communities of practice the way forward in changing the training culture in pharmacy?
Authors: Hindi Ali M. K. , Willis Sarah C. , Schafheutle Ellen I. 
Published: January 2022

Abstract
Background
Currently, there is little experiential learning in general practice (GP) during UK undergraduate and postgraduate pharmacy education and training.

Aim
To apply educational theories to explore pharmacy stakeholders’ perceptions of placements in general practice and contribute to the development of a model of experiential learning for pharmacy.

Methods
Qualitative, semi-structured interviews, conducted as part of two studies exploring experiential learning in general practice, with learners and their GP based supervisors. Interviews explored experiences of learning and practice, and what aided or hindered this. An abductive approach to analysis combined inductive coding with deductive, theory-driven interpretation using Lave and Wenger’s concept of “Communities of Practice”.

Results
Forty-four interviews were conducted, with learners and placement supervisors. Participants valued placements for providing authentic patient-facing learning experiences in the workplace, facilitated through legitimate peripheral participation by supervisors and supported by the use of pre- and de-briefing. Learners benefitted from support from their supervisor(s) and other staff during their day-to-day learning (informal learning), whilst also having protected time with their supervisors to discuss learning needs or go through workplace-based assessments (formal learning). Lack of clarity regarding which and how competencies should be assessed / demonstrated in general practice challenged monitoring progress from peripheral to full participation.
Findings suggest that GP placements provide opportunities for learning about the patient journey between care settings; to work effectively with multidisciplinary teams; and consolidation and application of consultation / communication skills learning.

Conclusions
The learning culture of GP supports learners’ development, providing time and opportunities for meaningful and authentic workplace learning, with healthcare professionals acting as supervisors and mentors. These findings can usefully inform implementation of meaningful learning opportunities in primary and secondary care for those involved in pharmacy education and training.
Clinical insights into the three-dimensional anatomy of cheek teeth in alpacas based on micro-computed tomography - Part 2: Maxillary cheek teeth
Authors: Proost Kirsten , Boone Matthieu N. , Josipovic Ivàn , Pardon Bart , Chiers Koen , Vlaminck Lieven 
Published: January 2022

AbstractBackgroundScientific knowledge regarding alpaca dentistry is relatively limited despite its clinical implications. The present gap in available supportive data leads to limited treatment options for dental pathology in alpacas in comparison to other species. The main goal of this study was to gain novel insights into the general and pulp morphology of maxillary cheek teeth to allow development of more advanced treatment strategies in the future. Also, the risk of causing pulp exposure when floating maxillary cheek teeth was of particular interest. Concurent research focusing on the anatomy of mandibular cheek teeth has been performed accordingly. The results obtained in mandibular teeth are expected to be non-extrapolatable because of the structural differences between mandibular and maxillary teeth.ResultsPulp morphology of maxillary cheek teeth showed great variation. A common pulp chamber was identified in 46/83 (55.4%) teeth with a mean dental age of 2 years and 7 months (± 2 years and 5 months). Pulpal segmentation was more commonly observed in teeth of increasing age. Full columnar segmentation was seen in 33/69 teeth (47.8%), whereas within-column segmentation was observed in 36/83 teeth (43.4%). Age and degree of segmentation of the pulpal tissue varied greatly according to Triadan position. Physical contact between roots of adjacent teeth was found in the majority of examined molars (range 82–94%) which resulted in morphological adaptations at the level of the root tips. The measured sub-occlusal dentinal thickness was as low as 0.46 mm above pulp horn 2 in a 14 years and 11 months old Triadan 09, emphasizing the risk of pulp exposure attributed to dental floating.ConclusionThis study offers an objective description of age-dependent maxillary cheek teeth pulp morphology in alpacas. Current findings are of great value to provide a basis for the development of tooth-saving techniques as a treatment for dental disease in this species. Observed physical contact between the roots of different examined molars may be a facilitating factor in the spread of apical infection in chronically diseased cases. Finally, a conservative approach regarding dental floating is recommended in order to avoid iatrogenic damage to pulp tissue.
Canine transmissible venereal tumour established in immunodeficient mice reprograms the gene expression profiles associated with a favourable tumour microenvironment to enable cancer malignancy
Authors: Ke Chiao-Hsu , Tomiyasu Hirotaka , Lin Yu-Ling , Huang Wei-Hsiang , Huang Hsiao-Hsuan , Chiang Hsin-Chien , Lin Chen-Si 
Published: January 2022

Abstract
Background
Canine transmissible venereal tumours (CTVTs) can cross the major histocompatibility complex barrier to spread among dogs. In addition to the transmissibility within canids, CTVTs are also known as a suitable model for investigating the tumour–host immunity interaction because dogs live with humans and experience the same environmental risk factors for tumourigenesis. Moreover, outbred dogs are more appropriate than inbred mice models for simulating the diversity of human cancer development. This study built a new model of CTVTs, known as MCTVTs, to further probe the shaping effects of immune stress on tumour development. For xenotransplantation, CTVTs were first injected and developed in immunodeficient mice (NOD.CB17-Prkdcscid/NcrCrl), defined as XCTVTs. The XCTVTs harvested from NOD/SCID mice were then inoculated and grown in beagles and named mouse xenotransplantation of CTVTs (MCTVTs).

Results
After the inoculation of CTVTs and MCTVTs into immune-competent beagle dogs separately, MCTVTs grew faster and metastasized more frequently than CTVTs did. Gene expression profiles in CTVTs and MCTVTs were analysed by cDNA microarray to reveal that MCTVTs expressed many tumour-promoting genes involved in chronic inflammation, chemotaxis, extracellular space modification, NF-kappa B pathways, and focal adhesion. Furthermore, several well-known tumour-associated biomarkers which could predict tumour progression were overexpressed in MCTVTs.

Conclusions
This study demonstrated that defective host immunity can result in gene instability and enable transcriptome reprogramming within tumour cells. Fast tumour growth in beagle dogs and overexpression of tumour-associated biomarkers were found in a CTVT strain previously established in immunodeficient mice. In addition, dysregulated interaction of chronic inflammation, chemotaxis, and extracellular space modification were revealed to imply the possibly exacerbating mechanisms in the microenvironments of these tumours. In summary, this study offers a potential method to facilitate tumour progression and provide a niche for discovering tumour-associated biomarkers in cancer research.
Toxoplasma gondii infection in pet cats and their owners in northeastern China:an important public health concern
Authors: Li Xin-Tong , Wang Lu , Ding Yuan , Sun Wu-Wen 
Published: January 2022

Abstract
Background
Limited information about Toxoplasma gondii infection in pet cats and their owners is available in China.

Methods
In this study, blood samples were randomly collected from 306 pet cats and 397 corresponding pet owners in Jilin province, northeastern China. Sera from the pet cats and the pet owners were tested for anti-T. gondii antibodies using an modified agglutination test (MAT) and an enzyme-linked immunosorbent assay (ELISA), respectively. Moreover, the risk factors for T. gondii infection in pet cats and corresponding pet owners were explored.

Result
In total, 62 sera out of 306 examined pet cats (20.3%) and 18.1% (72/397) pet cat owners were seropositive for T. gondii, respectively. The results of statistical analysis showed that both pet cats and their owners from rural area had significantly higher T. gondii seroprevalence than those from urban area (p < 0.001). Moreover, owners of pet cas who have the knowledge of zoonotic protozoan diseases had a significantly lower T. gondii seroprevalence than those without the knowledge of zoonotic protozoan diseases (p < 0.001).

Conclusions
The present results revealed that the seroprevalence of T. gondii infection are widespread in pet cats and their owners in Jilin province, northeastern China. Residence area and understanding knowledge of zoonotic protozoan diseases are considered to be raleted to the T. gondii infection. Hence, it is necessary to highlight the dangers and protection methods of zoonotic protozoan diseases caused by pet cats, especially in rural area.
SCUBE3 downregulation modulates hepatocellular carcinoma by inhibiting CCNE1 via TGFβ/PI3K/AKT/GSK3β pathway
Authors: Xu Pan , Luo Aoran , Xiong Chuan , Ren Hong , Yan Liang , Luo Qiang 
Published: January 2022

Abstract
Objectives
We aimed to verify the role of signal peptide-CUB-EGF-like domain-containing protein3 (SCUBE3) in the hepatocellular carcinoma (HCC) progression.

Methods
The role of SCUBE3 in HCC cell proliferation, apoptosis, and cell cycle in vitro were detected using MTT assay, colony formation assay, 5-ethynyl-2´-deoxyuridine assay (EDU), Celigo cell counting assay, Caspase3/7 activity assay, and flow cytometry. The effect of SCUBE3 on HCC cell proliferation in vivo was inspected by a xenograft tumour model in nude mice. The related mechanisms were further studied.

Results
The level of SCUBE3 was upregulated in HCC tissues and cell lines. Knockdown of SCUBE3 inhibited proliferation, promoted apoptosis, and induced cell cycle arrest in HCC cell lines in vitro and in vivo. Screening of cell cycle-related proteins revealed that CCNL2, CDK6, CCNE1, and CCND1 exhibited a significantly different expression profile. We found that SCUBE3 may promote the proliferation of HCC cells by regulating CCNE1 expression. The pathway enrichment analysis showed that the TGFβ signalling pathway and the PI3K/AKT signalling pathway were significantly altered. Co-immunoprecipitation results showed that SCUBE3 binds to the TGFβRII receptor. SCUBE3 knockdown inhibited the PI3K/AKT signalling pathway and the phosphorylation of GSK3β to inhibit its kinase activity.

Conclusions
SCUBE3 promotes HCC development by regulating CCNE1 via TGFβ/PI3K/AKT/GSK3β pathway. In addition, SCUBE3 may be a new molecular target for the clinical diagnosis and treatment of HCC.
circCDYL2 promotes trastuzumab resistance via sustaining HER2 downstream signaling in breast cancer
Authors: Ling Yun , Liang Gehao , Lin Qun , Fang Xiaolin , Luo Qing , Cen Yinghuan , Mehrpour Maryam , Hamai Ahmed , Liu Zihao , Shi Yu , Li Juanmei , Lin Wanyi , Jia Shijie , Yang Wenqian , Liu Qiang , Song Erwei , Li Jun , Gong Chang 
Published: January 2022

Abstract
Background
Approximate 25% HER2-positive (HER2+) breast cancer (BC) patients treated with trastuzumab recurred rapidly. However, the mechanisms underlying trastuzumab resistance remained largely unclear.

Methods
Trastuzumab-resistant associated circRNAs were identified by circRNAs high-throughput screen and qRT-PCR in HER2+ breast cancer tissues with different trastuzumab response. The biological roles of trastuzumab-resistant associated circRNAs were detected by cell vitality assay, colony formation assay, Edu assay, patient-derived xenograft (PDX) models and orthotopic animal models. For mechanisms research, the co-immunoprecipitation, Western blot, immunofluorescence, and pull down assays confirmed the relevant mechanisms of circRNA and binding proteins.

Results
We identified a circRNA circCDYL2, which was overexpressed in trastuzumab-resistant patients, which conferred trastuzumab resistance in breast cancer cells in vitro and in vivo. Mechanically, circCDYL2 stabilized GRB7 by preventing its ubiquitination degradation and enhanced its interaction with FAK, which thus sustained the activities of downstream AKT and ERK1/2. Trastuzumab-resistance of HER2+ BC cells with high circCDYL2 could be reversed by FAK or GRB7 inhibitor. Clinically, HER2+ BC patients with high levels of circCDYL2 developed rapid recurrence and had shorter disease-free survival (DFS) and overall survival (OS) following anti-HER2 therapy compared to those with low circCDYL2.

Conclusions
circCDYL2-GRB7-FAK complex plays a critical role in maintaining HER2 signaling, which contributes to trastuzumab resistance and circCDYL2 is a potential biomarker for trastuzumab-resistance in HER2+ BC patients.
Dysbiosis of vaginal microbiota associated with persistent high-risk human papilloma virus infection
Authors: Mei Ling , Wang Tao , Chen Yueyue , Wei Dongmei , Zhang Yueting , Cui Tao , Meng Jian , Zhang Xiaoli , Liu Yuqing , Ding Lisha , Niu Xiaoyu 
Published: January 2022

Abstract
Background
The status of vaginal microbiota in persistent high-risk human papilloma virus (HR-HPV) infection is unclear. The present work aimed to identify the vaginal microbiota of persistent HPV infection and explore the possible underlying microbiota factors.

Methods
A total of 100 women were recruited in this study, of which 28 presented HR-HPV persistent infection (P group), 30 showed clearance of any subtype of HR-HPV (C group), and 42 had no history of any HR-HPV infection (NC group). The vaginal microbiota and the community structure of the three groups were compared based on the 16S rRNA sequencing of the V3–V4 region. The microbiota diversity and differential analysis were carried out to detect the potential factors associated with HR-HPV infection.

Results
P and C groups showed an increase of Firmicutes and Actinobacteriota but a decrease in Proteobacteria compared to the NC group. The Chao1 index indicated that the microbial richness of the NC group was greater than C group (P < 0.05).The principal co-ordinate analysis(PCoA) revealed differences between the NC and P/C groups.The linear discriminant analysis effect size (LEfSe) method indicated that Proteobacteria phylum was significantly different in the mean relative abundance in the NC group,but the P and C groups did not show such indicative taxa. The Wilcox rank-sum test indicated that the Bifidobacterium (P = 0.002) and Lactobacillus (P = 0.005) of the C group were in a high mean relative abundance compared to the NC group.

Conclusions
The persistent HR-HPV infection is associated with dysbiosis of the vaginal microbiota. Microbiome regulation with Bifidobacteria and Lactobacillus may affect the clearance of HPV.
Increased expression of six-large extracellular vesicle-derived miRNAs signature for nonvalvular atrial fibrillation
Authors: Siwaponanan Panjaree , Kaewkumdee Pontawee , Phromawan Wilasinee , Udompunturak Suthipol , Chomanee Nusara , Udol Kamol , Pattanapanyasat Kovit , Krittayaphong Rungroj 
Published: January 2022

Abstract
Backgrounds
Non-valvular atrial fibrillation (AF) is the most common type of cardiac arrhythmia. AF is caused by electrophysiological abnormalities and alteration of atrial tissues, which leads to the generation of abnormal electrical impulses. Extracellular vesicles (EVs) are membrane-bound vesicles released by all cell types. Large EVs (lEVs) are secreted by the outward budding of the plasma membrane during cell activation or cell stress. lEVs are thought to act as vehicles for miRNAs to modulate cardiovascular function, and to be involved in the pathophysiology of cardiovascular diseases (CVDs), including AF. This study identified lEV-miRNAs that were differentially expressed between AF patients and non-AF controls.

Methods
lEVs were isolated by differential centrifugation and characterized by Nanoparticle Tracking Analysis (NTA), Transmission Electron Microscopy (TEM), flow cytometry and Western blot analysis. For the discovery phase, 12 AF patients and 12 non-AF controls were enrolled to determine lEV-miRNA profile using quantitative reverse transcription polymerase chain reaction array. The candidate miRNAs were confirmed their expression in a validation cohort using droplet digital PCR (30 AF, 30 controls). Bioinformatics analysis was used to predict their target genes and functional pathways.

Results
TEM, NTA and flow cytometry demonstrated that lEVs presented as cup shape vesicles with a size ranging from 100 to 1000 nm. AF patients had significantly higher levels of lEVs at the size of 101–200 nm than non-AF controls. Western blot analysis was used to confirm EV markers and showed the high level of cardiomyocyte expression (Caveolin-3) in lEVs from AF patients. Nineteen miRNAs were significantly higher (> twofold, p < 0.05) in AF patients compared to non-AF controls. Six highly expressed miRNAs (miR-106b-3p, miR-590-5p, miR-339-3p, miR-378-3p, miR-328-3p, and miR-532-3p) were selected to confirm their expression. Logistic regression analysis showed that increases in the levels of these 6 highly expressed miRNAs associated with AF. The possible functional roles of these lEV-miRNAs may involve in arrhythmogenesis, cell apoptosis, cell proliferation, oxygen hemostasis, and structural remodeling in AF.

Conclusion
Increased expression of six lEV-miRNAs reflects the pathophysiology of AF that may provide fundamental knowledge to develop the novel biomarkers for diagnosis or monitoring the patients with the high risk of AF.
The exit of axons and glial membrane from the developing Drosophila retina requires integrins
Authors: Ren Qian , Rao Yong 
Published: January 2022

AbstractCoordinated development of neurons and glia is essential for the establishment of neuronal circuits during embryonic development. In the developingDrosophilavisual system, photoreceptor (R cell) axons and wrapping glial (WG) membrane extend from the eye disc through the optic stalk into the optic lobe. Extensive studies have identified a number of genes that control the establishment of R-cell axonal projection pattern in the optic lobe. The molecular mechanisms directing the exit of R-cell axons and WG membrane from the eye disc, however, remain unknown. In this study, we show that integrins are required in R cells for the extension of R-cell axons and WG membrane from the eye disc into the optic stalk. Knockdown of integrins in R cells but not WG caused the stalling of both R-cell axons and WG membrane in the eye disc. Interfering with the function of Rhea (i.e. theDrosophilaortholog of vertebrate talin and a key player of integrin-mediated adhesion), caused an identical stalling phenotype. These results support a key role for integrins on R-cell axons in directing R-cell axons and WG membrane to exit the eye disc.
Long non-coding RNA lncC11orf54-1 modulates neuroinflammatory responses by activating NF-κB signaling during meningitic Escherichia coli infection
Authors: Xu Bojie , Yang Ruicheng , Yang Bo , Li Liang , Chen Jiaqi , Fu Jiyang , Qu Xinyi , Huo Dong , Tan Chen , Chen Huanchun , Peng Zhong , Wang Xiangru 
Published: January 2022

AbstractEscherichia coli is the most common gram-negative pathogenic bacterium causing meningitis. It penetrates the blood–brain barrier (BBB) and activates nuclear factor kappa B (NF-κB) signaling, which are vital events leading to the development of meningitis. Long non-coding RNAs (lncRNAs) have been implicated in regulating neuroinflammatory signaling, and our previous study showed that E. coli can induce differential expression of lncRNAs, including lncC11orf54-1, in human brain microvascular endothelial cells (hBMECs). The hBMECs constitute the structural and functional basis for the BBB, however, it is unclear whether lncRNAs are involved in the regulation of inflammatory responses of hBMECs during meningitic E. coli infection. In this study, we characterized an abundantly expressed lncRNA, lncC11orf54-1, which was degraded by translocated coilin to produce mgU2-19 and mgU2-30 in hBMECs during E. coli infection. Functionally, lncC11orf54-1-originated non-coding RNA mgU2-30 interacted with interleukin-1 receptor-associated kinase 1 (IRAK1) to induce its oligomerization and autophosphorylation, thus promoting the activation of NF-κB signaling and facilitating the production of pro-inflammatory cytokines. In summary, our study uncovers the involvement of lncC11orf54-1 in IRAK1–NF-κB signaling, and it functions as a positive regulator of inflammatory responses in meningitic E. coli-induced neuroinflammation, which may be a valuable therapeutic and diagnostic target for bacterial meningitis.