bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advance research directives: avoiding double standards
Authors: Heinrichs Bert 
Published: October 2021

Abstract
Background
Advance research directives (ARD) have been suggested as a means by which to facilitate research with incapacitated subjects, in particular in the context of dementia research. However, established disclosure requirements for study participation raise an ethical problem for the application of ARDs: While regular consent procedures call for detailed information on a specific study (“token disclosure”), ARDs can typically only include generic information (“type disclosure”). The introduction of ARDs could thus establish a double standard in the sense that within the context of ARDs, type disclosure would be considered sufficient, while beyond this context, token disclosure would remain necessary.

Main body
This paper provides an ethical analysis of ARDs, taking into account the results of numerous empirical studies that have been performed so far. It will be argued that a revised understanding of informed consent can allow for context-sensitive disclosure standards. As a consequence, ARDs that include type disclosure can be acceptable under suitable circumstances. Such an approach raises a number of objections. A thorough examination shows, however, that they are not sufficient to justify a rejection of the approach.

Conclusion
The approach presented in this paper avoids introducing a double standard. It is, therefore, more suitable for the implementation of ARDs than established approaches.
Evaluation of learning environment among Nursing undergraduates in state universities, Sri Lanka
Authors: Jayaweera Patalee , Thilakarathne Abisheka , Ratnayaka Madushanka , Shashikala Tharangi , Arachchige Rushani , Galgamuwa Lahiru Sandaruwan , Karunathilaka Nimantha , Amarasekara Thamara 
Published: October 2021

AbstractBackgroundThe learning environment is a vital part of the undergraduate curriculum which enable to delivery of quality education in the stipulated time. Therefore, this study aimed to evaluate the learning environment among BSc. Nursing undergraduates in Sri Lankan state universities.MethodsA descriptive cross-sectional study was conducted among 161 final year BSc. Nursing undergraduates in six state universities. Socio-demographic characteristics were collected using a self-administered questionnaire. The Dundee Ready Educational Environment Measure (DREEM) questionnaire was used to evaluate the learning environment in Perception of learning (SPL), Perceptions of teaching (SPT), Academic self-perceptions (SASP), Perceptions of the atmosphere (SPA), and Social self-perceptions (SSP). Based on the SPL, SPT, SASP, SPA, and SSP domains, the overall score of learning environment was ranged from 0 to 200 and then the overall score was classified into four categories such as poor (0–50), many problems (51–100), more positive than negative (101–150) and excellent (151–200). One-way Analysis of Variance (ANOVA) and t-test were used to determine the difference in the subscales and the overall scale.ResultsThe mean age of the students was 24.9 ± 0.9 years. The overall score of the learning environment was 127.1 ± 14.3. Student’s Perception of learning showed the highest mean score of 31.1 ± 3.9 while the social self-perception showed the lowest score (mean 16.4 ± 3.1). A significant group effect was observed in SPL and SPT subdomains among state universities while no significant group effect was observed in other subdomains. Furthermore, participating in extracurricular activities, travelling time to the faculty, and gender were observed as associated factors for the learning environment among BSc. Nursing undergraduates in state universities.ConclusionsAlthough the overall learning environment of BSc. Nursing undergraduates in state universities in Sri Lanka was within more positive than negative category, none of the university reaches to the excellent category. Therefore, each university should have improved their subdomains of learning environment to reach excellent category through addressing the gaps of curricular and extracurricular activities in the future.
Patients' assessment of care for type 2 diabetes: Results of the Patient Assessment of Chronic Illness Care scale in a Danish population
Authors: Frølich Anne , Nielsen Ann , Glümer Charlotte , Eriksen Christian U , Maindal Helle Terkildsen , Kleist Bodil Helbech , Birke Hanne , Stockmarr Anders 
Published: October 2021

Abstract
Background
The Patient Assessment of Chronic Illness Care (PACIC) scale is the most appropriate for assessing self-reported experience in chronic care. We aimed to validate the PACIC questionnaire by (1) assess patients’ perception of the quality of care for Danish patients with type 2 diabetes, (2) identify which factors are most important to the quality of care designated by the five subscales in PACIC, and (3) the validity of the questionnaire.

Methods
A survey of 7,745 individuals randomly selected from the National Diabetes Registry. Descriptive statistics inter-item and item-rest correlations and factor analysis assessed the PACIC properties. Quality of care was analysed with descriptive statistics; linear and multiple regression assessed the effect of forty-nine covariates on total and subscale scores.

Results
In total, 2,696 individuals with type 2 diabetes completed ≥ 50 % of items. The floor effect for individual items was 8.5–74.5 %; the ceiling effect was 4.1–47.8 %. Cronbach’s alpha was 0.73–0.86 for the five subscales. The comparative fit index (CFI) and the Tucker–Lewis index (TLI) were 0,87, and 0,84, respectively. Mean PACIC score was 2.44 (± 0.04). Respondents, who receive diabetes care primarily at general practice and outpatient clinics had higher scores compared to those receiving care at a private specialist. Receiving rehabilitation was followed by higher scores in all subscales. Those 70 years or older had lower mean total and subscale scores compared to younger patient groups.
A higher number of diabetes visits were associated with higher total scores; a higher number of emergency department visits were associated with lower total scores. The effects of healthcare utilisation on subscale scores varied.

Conclusions
These results provide insight into variations in the quality of provided care and can be used for targeting initiatives towards improving diabetes care. Factors important to the quality of perceived care are having a GP or hospital outpatient clinic as the primary organization. Also having a higher number of visits to the two organizations are perceived as higher quality of care as well as participating in a rehabilitation program. Floor and ceiling effects were comparable to an evaluation of the PACIC questionnaire in a Danish population. Yet, floor effects suggest a need for further evaluation and possible improvement of the PACIC questionnaire in a Danish setting. Total PACIC scores were lower than in other healthcare systems, possible being a result of different contexts and cultures, and of a need for improving diabetes care in Denmark.
A qualitative study on the implementation of a holistic care package for control and management of lymphoedema: experience from a pilot intervention in northern Ethiopia
Authors: Ali Oumer , Kinfe Mersha , Semrau Maya , Tora Abebayehu , Tesfaye Abraham , Mengiste Asrat , Davey Gail , Fekadu Abebaw 
Published: October 2021

Abstract
Background
Neglected Tropical Diseases (NTDs) such as podoconiosis, lymphatic filariasis (LF) and leprosy mainly affect communities in low resource settings. These diseases are associated with physical disability due to lymphoedema as well as poor mental health and psychosocial outcomes. Integration of care across these NTDs at primary health care level, which includes mental health and psychosocial care alongside physical health care, is increasingly recommended.

Methods
A holistic integrated care package was developed and piloted as part of the EnDPoINT project in Gusha district, Awi zone, Ethiopia. The intervention was conducted at the health care organization, health facility and community levels. To assess the impact of the care package in terms of acceptability, scalability, sustainability and barriers to implementation, a qualitative study was conducted in January 2020. This included four focus group discussions (29 participants) and ten key informant interviews with decision makers, health professionals, patients, and community representatives.

Results
The integrated lymphoedema care package was found to be efficient compared to vertical programs in saving time and resources. It also resulted in improved awareness of the causes, treatment and prevention of lymphoedema, in marked improvements in the lymphoedema, and in reduced stigma and discrimination. The care package was found to be acceptable to patients, health professionals and decision makers. The barriers to integrated care were unrealistic patient expectations, inadequate dissemination across health workers, and poor transportation access. Health professionals, decision makers and patients believed the integrated lymphoedema care package to be scalable and sustainable.

Conclusion
The integrated holistic care package was found to be acceptable to patients, health professionals and decision makers. We recommend its scale-up to other endemic districts.
Comparison of the accumulation of macro- and microelements in the bone marrow and bone of wild and farmed red deer (Cervus elaphus)
Authors: Tajchman Katarzyna , Ukalska-Jaruga Aleksandra , Bogdaszewski Marek , Pecio Monika , Janiszewski Pawel 
Published: October 2021

Abstract
Background
The cells of the entire body, including the skeletal system, especially of young animals, may derive from the bone marrow in which they multiply. Therefore, it is important to assess whether the diet and quality of life of deer have a significant impact on the elemental composition of bone and bone marrow, which can directly affect their health and growth. The aim of this study was to determine the concentrations of macro- (Ca, calcium, P, phosphorus, Mg, magnesium, K, potassium, Na, sodium) and microelements (Li, lithium, Cr, chromium, Mn, manganese, Co, cobalt, Cu, copper, Zn, zinc, Se, selenium, Mo, molybdenum, and Sn, tin) accumulated in the bone marrow and bones of deer (Cervus elaphus). The study was carried out on 15 young stags divided into two groups: farmed and wild animals. The concentrations of macro- and microelements were analysed using the inductively coupled plasma mass spectrometry technique. This research expands our knowledge on this topic, which so far has not been extensively studied.

Results
The mean content of K, Na, Zn and Se in the bone marrow of farmed animals was significantly higher than in wild deer, whereas the mean content of Ca, P, Mg, K, Na and Li in the bones was higher in wild animals than in farmed individuals (p < 0.05). In addition, the mean concentration of Cr, Mn, Cu, Se and Mo in the bones of the analysed animals differed significantly (p < 0.05) and was higher in the farmed deer. The mean concentration of Se in the bone marrow of wild deer decreased with the increase of the body weight (p < 0.05). In turn, the mean content of Mn in the bone marrow and of Mo in the bones of the animals was significantly positively correlated with the animals’ body weight (p < 0.05).

Conclusions
The obtained results indicated different levels of micro- and macro-components in the body of farmed and wild deer, though without clear and strong variations. Generally, the higher level of macronutrients in the bones of wild deer may be related to the higher physiological importance of these minerals for life activities in the natural environment and to the limited supply of balanced food. On the other hand, the higher levels of microelements in the tissues of farmed animals may result from their significantly better nutritional status in the first year of life, achieved through appropriate nutrition as well as diet supplementation of adult females.
Reciprocal deregulation of NKX3.1 and AURKA axis in castration-resistant prostate cancer and NEPC models
Authors: Sooreshjani Moloud Aflaki , Kamra Mohini , Zoubeidi Amina , Shah Kavita 
Published: October 2021

AbstractBackgroundNKX3.1, a prostate-specific tumor suppressor, is either genomically lost or its protein levels are severely downregulated, which are invariably associated with poor prognosis in prostate cancer (PCa). Nevertheless, a clear disconnect exists between its mRNA and protein levels, indicating that its post-translational regulation may be critical in maintaining its protein levels. Similarly, AURKA is vastly overexpressed in all stages of prostate cancer (PCa), including castration-resistant PCa (CRPC) and neuroendocrine PCa (NEPC), although its transcripts are only increased in ~ 15% of cases, hinting at additional mechanisms of deregulation. Thus, identifying the upstream regulators that control AURKA and NKX3.1’s levels and/or their downstream effectors offer an alternative route to inhibit AURKA and upregulate NKX3.1 in highly fatal CRPC and NEPC. AURKA and NKX3.1 have not linked to each other in any study to date.MethodsA chemical genetic screen revealed NKX3.1 as a direct target of AURKA. AURKA-NKX3.1 cross-talk was analyzed using several biochemical techniques in CRPC and NEPC cells.ResultsWe uncovered a reciprocal loop between AURKA and NKX3.1 in CRPC and NEPC cells. We observed that AURKA-mediated NKX3.1 downregulation is a major mechanism that drives CRPC pathogenesis and NEPC differentiation. AURKA phosphorylates NKX3.1 at three sites, which degrades it, but AURKA does not regulate NKX3.1 mRNA levels. NKX3.1 degradation drives highly aggressive oncogenic phenotypes in cells. NKX3.1 also degrades AURKA in a feedback loop. NKX3.1-AURKA loop thus upregulates AKT, ARv7 and Androgen Receptor (AR)-signaling in tandem promoting highly malignant phenotypes. Just as importantly, we observed that NKX3.1 overexpression fully abolished synaptophysin and enolase expression in NEPC cells, uncovering a strong negative relationship between NKX3.1 and neuroendocrine phenotypes, which was further confirmed be measuring neurite outgrowth. While WT-NKX3.1 inhibited neuronal differentiation, 3A-NKX3.1 expression obliterated it.ConclusionsNKX3.1 loss could be a major mechanism causing AURKA upregulation in CRPC and NEPC and vice versa. NKX3.1 genomic loss requires gene therapy, nonetheless, targeting AURKA provides a powerful tool to maintain NKX3.1 levels. Conversely, when NKX3.1 upregulation strategy using small molecules comes to fruition, AURKA inhibition should work synergistically due to the reciprocal loop in these highly aggressive incurable diseases.
Heterologous production of novel and rare C30-carotenoids using Planococcus carotenoid biosynthesis genes
Authors: Takemura Miho , Takagi Chiharu , Aikawa Mayuri , Araki Kanaho , Choi Seon-Kang , Itaya Mitsuhiro , Shindo Kazutoshi , Misawa Norihiko 
Published: October 2021

Abstract
Background
Members of the genus Planococcus have been revealed to utilize and degrade solvents such as aromatic hydrocarbons and alkanes, and likely to acquire tolerance to solvents. A yellow marine bacterium Planococcus maritimus strain iso-3 was isolated from an intertidal sediment that looked industrially polluted, from the Clyde estuary in the UK. This bacterium was found to produce a yellow acyclic carotenoid with a basic carbon 30 (C30) structure, which was determined to be methyl 5-glucosyl-5,6-dihydro-4,4′-diapolycopenoate. In the present study, we tried to isolate and identify genes involved in carotenoid biosynthesis from this marine bacterium, and to produce novel or rare C30-carotenoids with anti-oxidative activity in Escherichia coli by combinations of the isolated genes.

Results
A carotenoid biosynthesis gene cluster was found out through sequence analysis of the P. maritimus genomic DNA. This cluster consisted of seven carotenoid biosynthesis candidate genes (orf1–7). Then, we isolated the individual genes and analyzed the functions of these genes by expressing them in E. coli. The results indicated that orf2 and orf1 encoded 4,4′-diapophytoene synthase (CrtM) and 4,4′-diapophytoene desaturase (CrtNa), respectively. Furthermore, orf4 and orf5 were revealed to code for hydroxydiaponeurosporene desaturase (CrtNb) and glucosyltransferase (GT), respectively. By utilizing these carotenoid biosynthesis genes, we produced five intermediate C30-carotenoids. Their structural determination showed that two of them were novel compounds, 5-hydroxy-5,6-dihydro-4,4′-diaponeurosporene and 5-glucosyl-5,6-dihydro-4,4′-diapolycopene, and that one rare carotenoid 5-hydroxy-5,6-dihydro-4,4′-diapolycopene is included there. Moderate singlet oxygen-quenching activities were observed in the five C30-carotenoids including the two novel and one rare compounds.

Conclusions
The carotenoid biosynthesis genes from P. maritimus strain iso-3, were isolated and functionally identified. Furthermore, we were able to produce two novel and one rare C30-carotenoids in E. coli, followed by positive evaluations of their singlet oxygen-quenching activities.
High value-added products derived from crude glycerol via microbial fermentation using Yarrowia clade yeast
Authors: Rakicka-Pustułka Magdalena , Miedzianka Joanna , Jama Dominika , Kawalec Sylwia , Liman Kamila , Janek Tomasz , Skaradziński Grzegorz , Rymowicz Waldemar , Lazar Zbigniew 
Published: October 2021

Abstract
Background
Contemporary biotechnology focuses on many problems related to the functioning of developed societies. Many of these problems are related to health, especially with the rapidly rising numbers of people suffering from civilization diseases, such as obesity or diabetes. One factor contributing to the development of these diseases is the high consumption of sucrose. A very promising substitute for this sugar has emerged: the polyhydroxy alcohols, characterized by low caloric value and sufficient sweetness to replace table sugar in food production.

Results
In the current study, yeast belonging to the Yarrowia clade were tested for erythritol, mannitol and arabitol production using crude glycerol from the biodiesel and soap industries as carbon sources. Out of the 13 tested species, Yarrowia divulgata and Candida oslonensis turned out to be particularly efficient polyol producers. Both species produced large amounts of these compounds from both soap-derived glycerol (59.8–62.7 g dm−3) and biodiesel-derived glycerol (76.8–79.5 g dm−3). However, it is equally important that the protein and lipid content of the biomass (around 30% protein and 12% lipid) obtained after the processes is high enough to use this yeast in the production of animal feed.

Conclusions
The use of waste glycerol for the production of polyols as well as utilization of the biomass obtained after the process for the production of feed are part of the development of modern waste-free technologies.
EZR promotes pancreatic cancer proliferation and metastasis by activating FAK/AKT signaling pathway
Authors: Xu Jian , Zhang Wei 
Published: October 2021

AbstractBackgroundAs a member of the ERM (ezrin-radixin-moesin) protein family, EZR has been recognized as a regulator of adhesion signal pathways by researchers. Moreover, EZR was thought to play irreplaceable roles in invasion and metastasis of versatile cancers. In this study, we managed to undermine the effect of EZR on proliferation and metastasis in pancreatic cancer (PC).MethodsTo analyze the impact of EZR expression on overall survival and free diseases survival of PC patients, we screened abnormally expressed EZR in PC using the Gene Expression Omnibus database (GEO database) and The Cancer Genome Atlas (TCGA) database. Following, Gene Ontology (GO)-based functional analysis and Gene set enrichment analysis (GSEA) was performed to predicate the possible biological processes in which EZR were involved. The clinicopathological characteristics and prognosis of PC patients were analyzed according to clinical data. Further, immunohistochemistry, western blotting and real time PCR analysis were conducted to analyze the expression level of EZR in PC and paired paracancerous tissues. The effect of EZR on proliferation of PC cell lines were detected by Cell Counting Kit-8 assay, and meanwhile, Transwell assay was performed to detect the effect of EZR on invasion and migration of PC cell.ResultEZR exhibited higher expression level in pancreatic cancer tissues and cell than paracancerous tissues and cell, and its expression level was positively correlated with poor overall survival and diseases-free survival in PC patients. CCK8 assay indicated that EZR facilitated the proliferation of PC cells, meanwhile, Transwell assay showed that EZR promoted the migration and invasion of PC cells. The GO analysis predicated that EZR was involved in biological processes including cell adhesion, ameboidal-type cell migration, cell junction assembly. Through GSEA analysis, pancreatic cancer pathway, and the adhesion junction pathway were screened as the mostly enriched pathways in EZR-regulated pathological process. The inhibition of EZR suppressed proliferation and migration of PC cells. Western blot experiment revealed a positive correlation between EZR and FAK, the proliferation invasion and migration ability of PC cells were significantly decreased after knockdown of EZR.ConclusionOur finding revealed EZR accelerated the progression of PC via FAK/AKT signaling pathway.
Identification and validation of a pyroptosis-related prognostic signature for thyroid cancer
Authors: Wu Pu , Shi Jinyuan , Sun Wei , Zhang Hao 
Published: October 2021

Abstract
Background
Pyroptosis is a form of programmed cell death triggered by inflammasomes. However, the roles of pyroptosis-related genes in thyroid cancer (THCA) remain still unclear.

Objective
This study aimed to construct a pyroptosis-related signature that could effectively predict THCA prognosis and survival.

Methods
A LASSO Cox regression analysis was performed to build a prognostic model based on the expression profile of each pyroptosis-related gene. The predictive value of the prognostic model was validated in the internal cohort.

Results
A pyroptosis-related signature consisting of four genes was constructed to predict THCA prognosis and all patients were classified into high- and low-risk groups. Patients with a high-risk score had a poorer overall survival (OS) than those in the low-risk group. The area under the curve (AUC) of the receiver operator characteristic (ROC) curves assessed and verified the predictive performance of this signature. Multivariate analysis showed the risk score was an independent prognostic factor. Tumor immune cell infiltration and immune status were significantly higher in low-risk groups, which indicated a better response to immune checkpoint inhibitors (ICIs). Of the four pyroptosis-related genes in the prognostic signature, qRT-PCR detected three of them with significantly differential expression in THCA tissues.

Conclusion
In summary, our pyroptosis-related risk signature may have an effective predictive and prognostic capability in THCA. Our results provide a potential foundation for future studies of the relationship between pyroptosis and the immunotherapy response.