bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of network teaching in nursing undergraduate education during the coronavirus disease 2019 epidemic
Authors: Chen Xiuwen , Liu Shiqing , Tao Zirong , Ou Yangyang , Xiao Yao 
Published: April 2022

Abstract
Background and objectives
Coronavirus disease 2019 (COVID-19) is currently raging all over the world. COVID-19 can be transmitted among humans. To control the spread of the epidemic and meet the learning needs of students, Chinese universities have used a variety of multimedia forms to conduct online teaching. However, the influence of different teaching methods on the learning effects of nursing students has not been conclusive, and few studies have directly compared the differences in the effects of different teaching methods. Therefore, it is necessary to evaluate the impact of different teaching methods on students’ learning effects.

Methods
A total of 119 participants from the graduating class of 2022 performed 4 validated classes (fundamental nursing, medical nursing, surgical nursing, and paediatric nursing) through network teaching. A total of 126 participants from the graduating class of 2021 used the traditional teaching method and were enrolled as a control group. All participants completed a questionnaire, which was designed by the school for teaching evaluation, and took a test after the courses.

Results
A total of 245 nursing undergraduates were ultimately enrolled. The analysis of the academic performance and the student evaluations from the four courses showed no significant difference between the network teaching group and the traditional teaching group for nursing undergraduates (all P > 0.05).

Conclusion
Through the convenience of network teaching, teachers and students can choose the time and place of both their teaching and learning independently. Moreover, such use effectively prevents the spread of the epidemic. After the epidemic concludes, the continued use of the network teaching method can help improve teaching efficiency by being combined with the traditional teaching method.
Balancing standardisation and individualisation in transitional care pathways: a meta-ethnography of the perspectives of older patients, informal caregivers and healthcare professionals
Authors: Kvæl Linda Aimée Hartford , Hellesø Ragnhild , Bergland Astrid , Debesay Jonas 
Published: April 2022

Abstract
Background
Transitional care implies the transfer of patients within or across care settings in a seamless and safe way. For frail, older patients with complex health issues, high-quality transitions are especially important as these patients typically move more frequently within healthcare settings, requiring treatment from different providers. As transitions of care for frail people are considered risky, securing the quality and safety of these transitions is of great international interest. Nevertheless, despite efforts to improve quality in transitional care, research indicates that there is a lack of clear guidance to deal with practical challenges that may arise. The aim of this article is to synthesise older patients, informal caregivers and healthcare professionals’ experiences of challenges to achieving high-quality transitional care.

Methods
We used the seven-step method for meta-ethnography originally developed by Noblit and Hare. In four different but connected qualitative projects, the authors investigated the challenges to transitional care for older people in the Norwegian healthcare system from the perspectives of older patients, informal caregivers and healthcare professionals. In this paper, we highlight and discuss the cruciality of these challenging issues by synthesising the results from twelve articles.

Results
The analysis resulted in four themes: i) balancing person-centred versus efficient care, ii) balancing everyday patient life versus the treatment of illness, iii) balancing user choice versus “What Matters to You”, and iv) balancing relational versus practical care. These expressed challenges represent tensions at the system, organisation and individual levels based on partial competing assumptions on person-centred-care-inspired individualisation endeavours and standardisation requirements in transitional care.

Conclusions
There is an urgent need for a clearer understanding of the tension between standardisation and individualisation in transitional care pathways for older patients to ensure better healthcare quality for patients and more realistic working environments for healthcare professionals. Incorporating a certain professional flexibility within the wider boundary of standardisation may give healthcare professionals room for negotiation to meet patients’ individual needs, while at the same time ensuring patient flow, equity and evidence-based practice.
Failure mode effect and criticality analysis of ultrasound device by classification tracking
Authors: Wang Longchen , Li Bin , Hu Bing , Shen Guofeng , Zheng Yunxin , Zheng Yuanyi 
Published: April 2022

AbstractBackgroundMedical ultrasound device has been more and more widely used in the hospital and Its safety risk is significantly increased when failures occur. However, there is a lack of quantitative risk assessments of different types of failure modes for medical ultrasound device. This study utilizes a failure mode, effect and criticality analysis (FMECA) approach for quantitative risk evaluation of different failure modes for ultrasound devices.MethodsThe 4216 medical ultrasound device failure records at various hospitals were investigated. A failure mode and effect analysis method was developed for the quantitative evaluation of the risks of different failure modes. Visual correlation analysis was conducted for all categories to identify the causes of various failure modes. Based on the severity, occurrence and detectability of the failure causes determined, the risk priority number (RPN) for each failure mode was back-calculated through the obtained tracking diagram.ResultsThe failure modes of unclear images, unable to power on and dark shadows on an image had the highest RPNs. One failure mode could be caused by various factors, and the failure location was not necessarily related to the cause of the failure.ConclusionsThis quantitative approach more accurately evaluated the risks of different failure modes, and the results of the corresponding analysis of failure modes and causes could support the rapid determination of the causes of failures in clinical practice.
A versatile transposon-based technology to generate loss- and gain-of-function phenotypes in the mouse liver
Authors: Kopasz Anna Georgina , Pusztai Dávid Zsolt , Karkas Réka , Hudoba Liza , Abdullah Khaldoon Sadiq Ahmed , Imre Gergely , Pankotai-Bodó Gabriella , Migh Ede , Nagy Andrea , Kriston András , Germán Péter , Drubi Andrea Bakné , Molnár Anna , Fekete Ildikó , Dani Virág Éva , Ocsovszki Imre , Puskás László Géza , Horváth Péter , Sükösd Farkas , Mátés Lajos 
Published: April 2022

Abstract
Background
Understanding the contribution of gene function in distinct organ systems to the pathogenesis of human diseases in biomedical research requires modifying gene expression through the generation of gain- and loss-of-function phenotypes in model organisms, for instance, the mouse. However, methods to modify both germline and somatic genomes have important limitations that prevent easy, strong, and stable expression of transgenes. For instance, while the liver is remarkably easy to target, nucleic acids introduced to modify the genome of hepatocytes are rapidly lost, or the transgene expression they mediate becomes inhibited due to the action of effector pathways for the elimination of exogenous DNA. Novel methods are required to overcome these challenges, and here we develop a somatic gene delivery technology enabling long-lasting high-level transgene expression in the entire hepatocyte population of mice.

Results
We exploit the fumarylacetoacetate hydrolase (Fah) gene correction-induced regeneration in Fah-deficient livers, to demonstrate that such approach stabilizes luciferase expression more than 5000-fold above the level detected in WT animals, following plasmid DNA introduction complemented by transposon-mediated chromosomal gene transfer. Building on this advancement, we created a versatile technology platform for performing gene function analysis in vivo in the mouse liver. Our technology allows the tag-free expression of proteins of interest and silencing of any arbitrary gene in the mouse genome. This was achieved by applying the HADHA/B endogenous bidirectional promoter capable of driving well-balanced bidirectional expression and by optimizing in vivo intronic artificial microRNA-based gene silencing. We demonstrated the particular usefulness of the technology in cancer research by creating a p53-silenced and hRas G12V-overexpressing tumor model.

Conclusions
We developed a versatile technology platform for in vivo somatic genome editing in the mouse liver, which meets multiple requirements for long-lasting high-level transgene expression. We believe that this technology will contribute to the development of a more accurate new generation of tools for gene function analysis in mice.
Thyroid and endostyle development in cyclostomes provides new insights into the evolutionary history of vertebrates
Authors: Takagi Wataru , Sugahara Fumiaki , Higuchi Shinnosuke , Kusakabe Rie , Pascual-Anaya Juan , Sato Iori , Oisi Yasuhiro , Ogawa Nobuhiro , Miyanishi Hiroshi , Adachi Noritaka , Hyodo Susumu , Kuratani Shigeru 
Published: April 2022

Abstract
Background
The endostyle is an epithelial exocrine gland found in non-vertebrate chordates (amphioxi and tunicates) and the larvae of modern lampreys. It is generally considered to be an evolutionary precursor of the thyroid gland of vertebrates. Transformation of the endostyle into the thyroid gland during the metamorphosis of lampreys is thus deemed to be a recapitulation of a past event in vertebrate evolution. In 1906, Stockard reported that the thyroid gland in hagfish, the sister cyclostome group of lampreys, develops through an endostyle-like primordium, strongly supporting the plesiomorphy of the lamprey endostyle. However, the findings in hagfish thyroid development were solely based on this single study, and these have not been confirmed by modern molecular, genetic, and morphological data pertaining to hagfish thyroid development over the last century.

Results
Here, we showed that the thyroid gland of hagfish undergoes direct development from the ventrorostral pharyngeal endoderm, where the previously described endostyle-like primordium was not found. The developmental pattern of the hagfish thyroid, including histological features and regulatory gene expression profiles, closely resembles that found in modern jawed vertebrates (gnathostomes). Meanwhile, as opposed to gnathostomes but similar to non-vertebrate chordates, lamprey and hagfish share a broad expression domain of Nkx2-1/2-4, a key regulatory gene, in the pharyngeal epithelium during early developmental stages.

Conclusions
Based on the direct development of the thyroid gland both in hagfish and gnathostomes, and the shared expression profile of thyroid-related transcription factors in the cyclostomes, we challenge the plesiomorphic status of the lamprey endostyle and propose an alternative hypothesis where the lamprey endostyle could be obtained secondarily in crown lampreys.
GINS4 might be a novel prognostic immune-related biomarker of not only esophageal squamous cell carcinoma and other cancers
Authors: Jin Donghui , Yuan Ligong , Li Feng , Wang Shuaibo , Mao Yousheng 
Published: April 2022

Abstract
Background
Immunotherapy using immune checkpoint inhibitors (ICIs), such as antibody of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) has showed as a promising treatment for esophageal squamous cell carcinoma (ESCC), but resistance is unavoidable. This study aimed to find more immune-related genes to promote the efficiency of immunotherapy.

Materials and methods
Three datasets were downloaded from Gene Expression Omnibus (GEO) database. Gene differential analysis was performed to identify differentially expressed genes (DEGs), then ceRNA network was constructed based on differentially expressed lncRNAs and mRNAs. Next, Functional enrichment analysis and protein–protein interaction (PPI) network were built to reveal the potential function of mRNAs in ceRNA network. Survival analysis and immune cell infiltration level analysis were utilized to identify prognostic immune-related genes. Finally, pan-cancer analysis was performed to show the role of immune-related genes in other cancers.

Results
The data of 215 samples in total were obtained from GEO database (98 normal tissues and 117 tumor tissues), and 1685 differentially expressed mRNAs (176 downregulated and 1509 upregulated) and 3 upregulated lncRNAs (MCM3AP-AS1, HCP5 and GUSBP11, all upregulated) were found. ceRNA network was constructed to reveal some special correlation. Function enrichment showed some potential functions of mRNAs in ceRNA network such as mitotic cell cycle process, negative regulation of DNA-binding transcription factor activity, ossification, VEGFA-VEGFR2 signaling pathway, epithelial to mesenchymal transition, embryonic morphogenesis and so on. PPI network showed the physical interactions between each mRNA in ceRNA network. Through survival analysis and immune cell infiltration level analysis, GINS4 was confirmed as an immune-related prognostic gene in ESCC. GSEA showed some potential functions such as negative regulation of monocyte chemotaxis, antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, positive regulation of antigen processing and presentation, dendritic cell antigen processing and presentation and so on. Finally, pan-cancer analysis revealed that GINS4 might be a novel immune-related prognostic gene in ESCC and other cancers.

Conclusion
Our study suggested that GINS4 was correlated with prognosis and immune cell infiltration level of ESCC and other cancers. It may deserve further investigation as a potential immune-related prognostic biomarker of ESCC and other cancers.
Gonadotropins treatment prior to microdissection testicular sperm extraction in non-obstructive azoospermia: a single-center cohort study
Authors: Peng Tianwen , Liao Chen , Ye Xin , Chen Zhicong , Lan Yu , Fu Xin , An Geng 
Published: April 2022

AbstractBackgroundMicrodissection testicular sperm extraction (micro-TESE) in combination with ICSI can make paternity possible for non-obstructive azoospermia (NOA) patients. Testicular sperm can be successfully retrieved in nearly half of NOA patients. Nevertheless, not many convincing protocols are established to improve sperm retrieval rate (SRR). The goal of this study was to evaluate whether gonadotropins therapy before micro-TESE could improve sperm retrieval rate and affect the ICSI outcomes in non-obstructive azoospermia patients with hypergonadotropic hypogonadism.MethodsThis retrospective cohort study included a total of 569 non-obstructive azoospermia men who underwent micro-TESE with or without 3-month of preoperative hCG / hCG plus highly purified urinary FSH (uFSH) between January 2016 and December 2019. The primary outcome was the sperm retrieval rate of micro-TESE.ResultsSperm was found in 27 patients among 395 NOA men who accepted preoperative gonadotropins treatment (6.8%, 27/395) in post-treatment semen analysis for ICSI. One hundred forty nine out of 542 patients could successfully obtain enough sperm for ICSI through the micro-TESE (overall SRR = 27.5%). There was a statistically significant difference in the SRR between the preoperative gonadotropins treatment and non-gonadotropins treatment groups (31.2%, 115/368 vs. 19.5%, 34/174,P = 0.006). In the multivariable analysis with IPTW according to the propensity score, there was a significant association between preoperative gonadotropins treatment and the SRR (OR, 1.59; 95% CI: 1.02–2.52;P = 0.042). No differences in the clinical pregnancy rate, live birth delivery rate, or miscarriage rate were observed between the two groups.ConclusionPreoperative gonadotropins therapy seems to have a role in improving SRR in NOA patients with hypergonadotropic hypogonadism. We found that gonadotropins therapy had no effect on ICSI clinical outcomes and live birth.
A simple approach to assess the cancer risk of occupational exposure to genotoxic drugs in healthcare settings
Authors: Gerding Johannes , Anhäuser Lea , Eickmann Udo , Nienhaus Albert 
Published: April 2022

Abstract
Background
Several drugs for human use possess genotoxic properties as a necessary consequence of their intended therapeutic effect (e.g. antineoplastics). Health workers may be exposed to these chemicals in various occupational settings such as dose preparation and administration. To date, there are no quantitative risk assessment models to estimate the cancer risk of health workers due to the handling of genotoxic drugs. We therefore developed a quantitative risk assessment model to assess the cancer risk of occupational exposure to genotoxic drugs in healthcare settings based on the threshold of toxicological concern (TTC) concept. This model was used to evaluate the cancer risk of health workers due to the handling of genotoxic drugs in modern health care facilities.

Methods
We modified the threshold of toxicological concern (TTC) concept to fit the purpose of occupational cancer risk assessment. The risk model underlying ICH guideline M7 (R1): “assessment and control of DNA reactive (mutagenic) impurities in pharmaceuticals to limit potential carcinogenic risk” was used as a starting point for our model. We conducted a short review of studies on the occupational exposure of health workers to genotoxic drugs. These occupational exposure data were compared to the acceptable exposure levels resulting from our TTC based risk model.

Results
Based on the threshold of toxicological concern (TTC) concept, we defined an acceptable daily intake (ADI) of 4 μg/day as threshold of no concern for the exposure of health workers to genotoxic drugs. Regarding the dermal exposure of health workers to genotoxic drugs, we derived a corresponding acceptable surface contamination level (ASCL) of 20 ng/cm2. Both ADI and ASCL are usually not exceeded in modern healthcare settings. Current safety precautions provide sufficient protection to health workers.

Conclusions
The application of our model indicates that workers in modern healthcare facilities are not at risk of developing work related cancer above widely accepted cancer risk levels due to the occupational exposure to genotoxic drugs. Hence, the present study may assist employers and public authorities to make informed decisions concerning the need for (further) protective measures and during risk communication to health workers.
The roles of CC chemokines in response to radiation
Authors: Wang Lei , Jiang Jizong , Chen Yuan , Jia Qingzhu , Chu Qian 
Published: April 2022

AbstractRadiotherapy is an effective regimen for cancer treatment alone or combined with chemotherapy or immunotherapy. The direct effect of radiotherapy involves radiation-induced DNA damage, and most studies have focused on this area to improve the efficacy of radiotherapy. Recently, the immunomodulatory effect of radiation on the tumour microenvironment has attracted much interest. Dying tumour cells can release multiple immune-related molecules, including tumour-associated antigens, chemokines, and inflammatory mediators. Then, immune cells are attracted to the irradiated site, exerting immunostimulatory or immunosuppressive effects. CC chemokines play pivotal roles in the trafficking process. The CC chemokine family includes 28 members that attract different immune subsets. Upon irradiation, tumour cells or immune cells can release different CC chemokines. Here, we mainly discuss the importance of CCL2, CCL3, CCL5, CCL8, CCL11, CCL20 and CCL22 in radiotherapy. In irradiated normal tissues, released chemokines induce epithelial to mesenchymal transition, thus promoting tissue injury. In the tumour microenvironment, released chemokines recruit cancer-associated cells, such as tumour-infiltrating lymphocytes, myeloid-derived suppressor cells and tumour-associated macrophages, to the tumour niche. Thus, CC chemokines have protumour and antitumour properties. Based on the complex roles of CC chemokines in the response to radiation, it would be promising to target specific chemokines to alleviate radiation-induced injury or promote tumour control.
The protective effect of kirenol in osteoarthritis: an in vitro and in vivo study
Authors: Hu Wei , Mao Chao , Sheng Weibin 
Published: April 2022

Abstract
Background
Osteoarthritis (OA) is a chronic degenerative disease, its main characteristic involves articular cartilage destruction and inflammation response, absent of effective medical treatment. Our current research aimed to explore anti-inflammatory effect of kirenol, a diterpenoid natural product compound, in the development of OA and its potential molecular mechanism through in vitro and in vivo study.

Methods
In vitro, chondrocytes were pretreated with kirenol for 2 h before IL-1β stimulation. Production of NO, PGE2, TNF-α, IL-6, aggrecan, collagen-II, MMP13and ADAMTS5 were evaluated by the Griess reaction and ELISAs. The mRNA (aggrecan and collagen-II) and protein expression (COX-2, iNOS, P65, IκB, PI3K, AKT) were measured by qRT-PCR and Western blot respectively. Immunofluorescence was used to assess the expression of collagen-II and P65. The in vivo effect of kirenol was evaluated in mice OA models induced by destabilization of the medial meniscus (DMM).

Results
We found that kirenol inhibited IL-1β-induced expression of NO, PGE2, TNF-α, IL-6, COX-2, iNOS, ADAMTS-5. Besides, kirenol remarkably decreased IL-1β-induced degradation of aggrecan and collagen-II. Furthermore, kirenol significantly inhibited IL-1β-induced phosphorylation of PI3K/Akt and NF-κB signaling. In vivo, the cartilage in kirenol-treated mice exhibited less cartilage degradation and lower OARSI scores.

Conclusions
Taken together, the results of this study provide potent evidence that kirenol could be utilized as a potentially therapeutic agent in prevention and treatment of OA.