bluuebunny/crossref_metadata_2025_split huggingface dataset:
Involving clinicians in management: assessing views of doctors and nurses on hybrid professionalism in clinical directorates
Authors: Prenestini Anna , Sartirana Marco , Lega Federico 
Published: April 2021

Abstract
Background
Hybrid professionalism is one of the most effective ways to involve clinicians in management practices and responsibilities. With this study we investigated the perceptions of doctors and nurses on hybridization in clinical directorates (CDs) in hospitals.

Methods
We investigated the attitudes of healthcare professionals (doctors and nurses) towards eight hospital CDs in the Local Health Authority (LHA) of Bologna (Emilia Romagna, Italy) 6 years after their implementation. We used a validated questionnaire by Braithwaite and Westbrook (2004). Drawing on Palmer et al. (2007), we added a section about the characteristics of department heads. In all, 123 healthcare professionals in managerial roles completed and returned the questionnaire. The return rate was 47.4% for doctors and 31.6% for nurses.

Results
Doctors reported an increase in clinical governance, interdisciplinarity collaboration, and standardization of clinical work. Hybridization of practices was noted to have taken place. While doctors did not see these changes as a threat to professional values, they felt that hospital managers had taken greater control. There was a large overlap of attitudes between doctors and nurses: inter-professional integration in CDs fostered alignment of values and aims. The polarity index was higher for responses from the doctors than from the nurses.

Conclusion
The study findings have implications for policy makers and managers: mission and strategic mandate of CDs; governance of CDs, leadership issues; opportunities for engaging healthcare professionals; changes in managerial involvement during the COVID-19 pandemic. We also discuss the limitations of the present study and future areas for research into hybrid structures.
Breastfeeding and the risk of childhood cancer: a systematic review and dose-response meta-analysis
Authors: Su Qing , Sun Xiaohui , Zhu Liwen , Yan Qin , Zheng Peiwen , Mao Yingying , Ye Ding 
Published: April 2021

AbstractBackgroundThe aim of this study was to quantitatively summarize the available evidence on the association of breastfeeding with the risk of childhood cancer.MethodsA literature search of PubMed and Embase databases was performed to identify eligible observational studies published from inception to July 17, 2020. The categorical and dose-response meta-analysis was conducted by pooling relative risk (RR) or odds ratio (OR) estimates with 95% confidence intervals (CIs). Potential sources of heterogeneity were detected by meta-regression and stratification analysis. Sensitivity analysis and publication bias test were also carried out.ResultsForty-five articles involving 475,579 individuals were included in the meta-analysis. Among the thirty-three studies on the association between breastfeeding and risk of childhood leukemia, the pooled risk estimates were 0.77 (95% CI, 0.65–0.91) and 0.77 (95% CI 0.63–0.94) for ever versus non/occasional breastfeeding and longest versus shortest breastfeeding duration group, respectively. There was clear indication for non-linear dose-response relationship between breastfeeding duration and the risk of childhood leukemia (Pnon-linear < 0.001). The most protective effect (OR, 0.66, 95% CI 0.62–0.70) was observed at a breastfeeding duration of 9.6 months. Four studies examined, the association between breastfeeding and risk of childhood neuroblastoma, and significant inverse associations were consistently observed in both the comparisons of ever breastfeeding versus non/occasional breastfeeding (OR = 0.59, 95% CI 0.44–0.81) and longest versus shortest breastfeeding (OR = 0.61, 95% CI 0.44–0.83). However, no associations of breastfeeding with risk of other cancers were found.ConclusionsOur study supports a protective role of breastfeeding on the risk of childhood leukemia, also suggesting a non-linear dose-response relationship. Further studies are warranted to confirm the association between breastfeeding and risk of childhood neuroblastoma.
Identification and genetic characterization of equine infectious anemia virus in Western Balkans
Authors: Lupulovic Diana , Savić Sara , Gaudaire Delphine , Berthet Nicolas , Grgić Živoslav , Matović Kazimir , Deshiere Alexandre , Hans Aymeric 
Published: April 2021

Abstract
Background
Equine infectious anemia (EIA) is a viral disease, caused by the Equine Infectious Anemia virus (EIAV) belonging to the Retroviridae family, genus Lentivirus. Horses (or equids) infected with EIAV are lifelong carriers and they remain contagious for other horses even in the absence of clinical signs. So far, EIAV infection has been reported among horses in North and South America, France, Germany, Italy, Hungary and Romania, with no publication regarding the presence of EIAV in horses in Serbia. To determine the circulation of EIAV among, approximately, the 5000 horses of the Vojvodina region, northern part of Serbia, 316 serum undergone serological testing for EIA. Then, identification and full genome sequencing using next generation sequencing was performed from one EIA positive horse.

Results
the 316 sera were tested with 3 different commercial agar gel immunodiffusion (AGID) tests and two different commercial enzyme-linked immunosorbent assay (ELISA). With the three AGID kits, 311 (98.4%) among the 316 tested sera were negative and only five (1.6%) sera were positive for EIA. Some discrepancies were seen for the two ELISA kits tested since one exhibited the same results as AGID test and the second gave 295 sera with negative results, five with a positive result and 16 with doubtful outcome. Phylogenetic analysis performed using the full genome sequence showed that EIAV characterized from a horse in Serbia is different from those identify so fare around the world and form a distinct and separate group together with another EIAV strain.

Conclusions
This study demonstrate for the first time that EIAV is circulating at a low level in the horse population from the Northern part of Serbia. Interestingly, phylogenetic data indicates that this EIAV from the western Balkan region of Europe belongs to a new cluster.
Serological evidence of Rift Valley fever virus infection among domestic ruminant herds in Uganda
Authors: Ndumu Deo B. , Bakamutumaho Barnabas , Miller Edward , Nakayima Jesca , Downing Robert , Balinandi Stephen , Monje Fred , Tumusiime Dan , Nanfuka Mary , Meunier Natascha , Arinaitwe Eugene , Rutebarika Chris , Kidega Eugene , Kyondo Jackson , Ademun Rose , Njenga Kariuki M. , Veas Francisco , Gonzalez Jean-Paul 
Published: April 2021

Abstract
Background
Prior to the first recorded outbreak of Rift Valley fever (RVF) in Uganda, in March 2016, earlier studies done until the 1970’s indicated the presence of the RVF virus (RVFV) in the country, without any recorded outbreaks in either man or animals. While severe outbreaks of RVF occurred in the neighboring countries, none were reported in Uganda despite forecasts that placed some parts of Uganda at similar risk.
The Ministry of Agriculture, Animal Industry and Fisheries (MAAIF) undertook studies to determine the RVF sero-prevalence in risk prone areas.
Three datasets from cattle sheep and goats were obtained; one from retrospective samples collected in 2010–2011 from the northern region; the second from the western region in 2013 while the third was from a cross-sectional survey done in 2016 in the south-western region. Laboratory analysis involved the use of the Enzyme Linked Immunosorbent Assays (ELISA). Data were subjected to descriptive statistical analyses, including non-parametric chi-square tests for comparisons between districts and species in the regions.

Results
During the Yellow Fever outbreak investigation of 2010–2011 in the northern region, a total sero-prevalence of 6.7% was obtained for anti RVFV reacting antibodies (IgG and IgM) among the domestic ruminant population. The 2013 sero-survey in the western region showed a prevalence of 18.6% in cattle and 2.3% in small ruminants. The 2016 sero-survey in the districts of Kabale, Kanungu, Kasese, Kisoro and Rubirizi, in the south-western region, had the respective district RVF sero-prevalence of 16.0, 2.1, 0.8, 15.1and 2.7% among the domestic ruminants combined for this region; bovines exhibited the highest cumulative sero-prevalence of 15.2%, compared to 5.3 and 4.0% respectively for sheep and goats per species for the region.

Conclusions
The absence of apparent outbreaks in Uganda, despite neighboring enzootic areas, having minimal restrictions to the exchange of livestock and their products across borders, suggest an unexpected RVF activity in the study areas that needs to be unraveled. Therefore, more in-depth studies are planned to mitigate the risk of an overt RVF outbreak in humans and animals as has occurred in neighboring countries.
Benign juvenile idiopathic epilepsy in captive Iberian lynx (Lynx pardinus) in the ex situ conservation program (2005–2019)
Authors: Mínguez Juan J. , El Bouyafrouri Yasmin , Godoy José A. , Rivas Antonio , Fernández Jesús , Asensio Victoria , Serra Rodrigo , Perez-Aspa María J. , Lorenzo Valentina 
Published: April 2021

Abstract
Background
Benign juvenile idiopathic epilepsy has been described in humans but rarely in animals. The objectives of the study were to describe the clinical signs, clinical data, imaging findings, genetic examinations, treatment, long-term outcome and prognosis in Iberian lynx with juvenile epilepsy. Medical records, video recordings and diagnostic data from 2005 to 2019 were reviewed.

Results
Twenty lynx cubs with early onset of epileptic seizures (ES) from the conservation program were included. The average age at seizure onset was 75 days. Isolated and cluster ES were recorded. Focal ES, focal ES evolving into generalized ES with a stereotypical pattern and generalized ES were observed. All the cubs were normal between episodes, had a normal neurological examination and unremarkable investigations. Phenobarbital was used as a first line antiepileptic drug (AED). ES halted 10 days (0–34) after starting treatment in eight out of twenty cubs (40%). Treatment was discontinued in this group after a mean of 578 days and no further ES were reported (mean follow-up longer than 5 years). Eleven animals (55%) continued on AED treatment for a mean of 1306 days (70–3466). An adult-onset was observed for one lynx (5%). Polytherapy was necessary in seven lynxes (35%). The inheritance pattern observed was compatible with an autosomal recessive condition. Based on this assumption, mating between two identified carriers has been avoided since 2012, which may have contributed to the subsequent decrease in prevalence, with no further cases detected in 2018 and 2019.

Conclusions
Lynx pardinus may have an early onset self-limiting ES syndrome characteristic of benign juvenile idiopathic epilepsy. Information obtained from this study strongly suggests a genetic basis for the here presented epilepsy.
Construction of a long noncoding RNA-based competing endogenous RNA network and prognostic signatures of left- and right-side colon cancer
Authors: Li Ke-zhi , Yin Yi-xin , Tang Yan-ping , Long Long , Xie Ming-zhi , Li Ji-lin , Ding Ke , Hu Bang-li 
Published: April 2021

Abstract
Background
Cancers located on the right and left sides of the colon have distinct clinical and molecular characteristics. This study aimed to explore the regulatory mechanisms of location-specific long noncoding RNAs (lncRNAs) as competing endogenous RNAs (ceRNAs) in colon cancer and identify potential prognostic biomarkers.

Method
Differentially expressed lncRNAs (DELs), miRNAs (DEMs), and genes (DEGs) between right- and left-side colon cancers were identified by comparing RNA sequencing profiles. Functional enrichment analysis was performed for the DEGs, and a ceRNA network was constructed. Associations between DELs and patient survival were examined, and a DEL-based signature was constructed to examine the prognostic value of these differences. Clinical colon cancer tissues and Gene Expression Omnibus (GEO) datasets were used to validate the results.

Results
We identified 376 DELs, 35 DEMs, and 805 DEGs between right- and left-side colon cancers. The functional enrichment analysis revealed the functions and pathway involvement of DEGs. A ceRNA network was constructed based on 95 DEL–DEM–DEG interactions. Three DELs (LINC01555, AC015712, and FZD10-AS1) were associated with the overall survival of patients with colon cancer, and a prognostic signature was established based on these three DELs. High risk scores for this signature indicated poor survival, suggesting that the signature has prognostic value for colon cancer. Examination of clinical colon cancer tissues and GEO dataset analysis confirmed the results.

Conclusion
The ceRNA regulatory network suggests roles for location-specific lncRNAs in colon cancer and allowed the development of an lncRNA-based prognostic signature, which could be used to assess prognosis and determine treatment strategies in patients with colon cancer.
MicroRNA-665 facilitates cell proliferation and represses apoptosis through modulating Wnt5a/β-Catenin and Caspase-3 signaling pathways by targeting TRIM8 in LUSC
Authors: Chen Tian-Jun , Zheng Qi , Gao Fei , Yang Tian , Ren Hui , Li Yang , Chen Ming-Wei 
Published: April 2021

Abstract
Background
MicroRNAs (miRNAs) are involved in the oncogenesis, development and transformation of lung squamous cell carcinoma (LUSC). miR-665 is clinically significant and acts as a pivotal function in some cancers. Nevertheless, the effects and the potential mechanisms of miR-665 in human LUSC are still unknown.

Methods
To analyse the clinical significant of miR-665 in human LUSC, quantitative real-time PCR (qRT-PCR) was use to measure miR-665 expression in LUSC specimen tissues and cell lines. Tripartite motif 8 (TRIM8) was verified a target of miR-665 by performing bioinformatic prediction and luciferase reporter assay. The expression levels of TRIM8 were examined through qRT-PCR and Western blotting in LUSC specimen tissues. CCK8 assay was fulfilled for analyzing the function in LUSC cell proliferation. Flow cytometry was used to detect cell and apoptosis. TRIM8 silencing and overexpression further verified the biological effects as those caused by miR-665.

Results
Here we reported that miR-665 expression was upregulated in LUSC specimen tissues and cell lines. High miR-665 levels were related to differentiation, tumor size and TNM stage. miR-665 mimics facilitated LUSC cell growth and cell cycle G1-S transition and repressed apoptosis. miR-665 inhibitor suppressed cell proliferation and G1-S transition and promoted apoptosis. miR-665 expression was negatively correlated with TRIM8 mRNA expression in LUSC. Luciferase reporter assay confirmed that TRIM8 was a direct target gene of miR-665. miR-665 mimics downregulated the TRIM8 levels, and miR-665 inhibitor upregulated the TRIM8 levels in LUSC cells. Particularly, silencing TRIM8 led to the similar effects of miR-665 mimics in LUSC cells. Overexpression of TRIM8 inhibited LUSC cell proliferation in vitro and in vivo. Furthermore, miR-665 promoted LUSC cell proliferation through facilitating the Wnt5a/β-catenin signaling pathway and restrained apoptosis via inhibiting Caspase-3 signaling pathway, whereas TRIM8 suppressed cell growth by repressing the Wnt5a/β-catenin signaling pathway and induced apoptosis through activating Caspase-3 signaling pathway.

Conclusions
The current study demonstrates that miR-665 facilitates LUSC cell proliferation and cell cycle transition by regulation of the Wnt5a/β-Catenin signaling pathway and represses cell apoptosis via modulation of Caspase-3 signaling pathway by directly targeting TRIM8. These findings suggest that miR-665 might be a potential new target for LUSC therapy.
Alkaline phosphatase downregulation promotes lung adenocarcinoma metastasis via the c-Myc/RhoA axis
Authors: Lou Zhefeng , Lin Weiwei , Zhao Huirong , Jiao Xueli , Wang Cong , Zhao He , Liu Lu , Liu Yu , Xie Qipeng , Huang Xing , Huang Haishan , Zhao Lingling 
Published: April 2021

Abstract
Background
Lung adenocarcinoma (LUAD) metastasis significantly reduces patient survival; hence inhibiting the metastatic ability of lung cancer cells will greatly prolong patient survival. Alkaline phosphatase (ALPL), a homodimeric cell surface phosphohydrolase, is reported to play a controversial role in prostate cancer and ovarian cancer cell migration; however, the function of ALPL in LUAD and the related mechanisms remain unclear.

Methods
TCGA database was used to analysis the expression of ALPL, and further verification was performed in a cohort of 36 LUAD samples by qPCR and western blot. Soft-agar assay, transwell assay and lung metastasis assay were employed to detect the function of ALPL in LUAD progression. The qPCR, luciferase promoter reporter assay and western blot were used to clarify the molecular mechanisms of ALPL in promoting metastasis in LUAD.

Results
ALPL was downregulated in LUAD, and the disease-free survival rate of patients with low ALPL was significantly reduced. Further studies showed that overexpression of ALPL in LUAD cell lines did not significantly affect cell proliferation, but it did significantly attenuate lung metastasis in a mouse model. ALPL downregulation in LUAD led to a decrease in the amount of phosphorylated (p)-ERK. Because p-ERK promotes the classical c-Myc degradation pathway, the decrease in p-ERK led to the accumulation of c-Myc and therefore to an increase in RhoA transcription, which enhanced LUAD cell metastasis.

Conclusion
ALPL specially inhibits the metastasis of LUAD cells by affecting the p-ERK/c-Myc/RhoA axis, providing a theoretical basis for the targeted therapy of clinical LUAD.
The biological function and clinical significance of STIL in osteosarcoma
Authors: Ji Shu-fan , Wen Sheng-Lian , Sun Yu , Huang Pi-wei , Wu Hao , He Mao-lin 
Published: April 2021

Abstract
Background
SCL/TAL1 interrupting locus (STIL) is associated with the progression of several tumors; however, the biological role of STIL in osteosarcoma remains poorly understood.

Methods
In this study, the clinical significance of STIL in osteosarcoma was analyzed by gene chip data recorded in public databases. STIL expression was silenced in osteosarcoma cell lines to observe the effects on proliferation, apoptosis, invasion, and migration. Differentially expressed genes (DEGs) in the osteosarcoma chip were analyzed using The Limma package, and STIL co-expressed genes were obtained via the Pearson correlation coefficient. The potential molecular mechanism of STIL in osteosarcoma was further explored by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways.

Results
Osteosarcoma was associated with higher STIL expression compared to the control samples, and the standardized mean difference (SMD) was 1.52. STIL also had a good ability to distinguish osteosarcoma from non-osteosarcoma samples [area under the curve (AUC) = 0.96]. After silencing STIL, osteosarcoma cell proliferation decreased, apoptosis increased, and the migratory and invasion ability decreased. A total of 294 STIL differentially co-expressed genes were screened, and a bioinformatics analysis found that differentially co-expressed genes were primarily enriched in the cell signaling pathways. The protein-protein interaction (PPI) network indicated that the hub differentially co-expressed genes of STIL were CDK1, CCNB2, CDC20, CCNA2, BUB1, and AURKB.

Conclusions
STIL is associated with osteosarcoma proliferation and invasion, and may be promote the progression of osteosarcoma by regulating the expression of CDK1, CCNB2, CDC20, CCNA2, BUB1 and AURKB.
Allelic diversity of merozoite surface protein genes (msp1 and msp2) and clinical manifestations of Plasmodium falciparum malaria cases in Aceh, Indonesia
Authors: Jamil Kurnia Fitri , Pratama Nandha Rizki , Marantina Sylvia Sance , Harapan Harapan , Kurniawan Muhammad Riza , Zanaria Tjut Mariam , Hutagalung Jontari , Rozi Ismail Ekoprayitno , Asih Puji Budi Setia , Supargiyono  , Syafruddin Din 
Published: April 2021

Abstract
Background
The malaria control programme in Indonesia has successfully brought down malaria incidence in many parts in Indonesia, including Aceh Province. Clinical manifestation of reported malaria cases in Aceh varied widely from asymptomatic, mild uncomplicated to severe and fatal complications. The present study aims to explore the allelic diversity of merozoite surface protein 1 gene (msp1) and msp2 among the Plasmodium falciparum isolates in Aceh Province and to determine their potential correlation with the severity of malaria clinical manifestation.

Methods
Screening of over 500 malaria cases admitted to the hospitals in 11 districts hospital within Aceh Province during 2013–2015, identified 90 cases of P. falciparum mono-infection without any co-morbidity. The subjects were clinically phenotyped and parasite DNA was extracted and polymerase chain reaction (PCR) amplified for the msp1 and msp2 allelic subfamilies.

Results
Analysis of clinical manifestation revealed that fever-chill is the most frequent symptom. Based on WHO criteria showed 19 cases were classified as severe and 71 as mild malaria. Analysis of msp1 gene revealed the presence of K1 allele subfamily in 34 subjects, MAD20 in 42 subjects, RO33 in 1 subject, and mixed allelic of K1 + MAD20 in 5 subjects, K1 + RO33 in 4 subjects, and MAD20 + RO33 in 4 subjects. Analysis of msp2 gene revealed 34 subjects carried the FC27 allelic subfamily, 37 subjects carried the 3D7 and 19 subjects carried the mixed FC27 + 3D7. Analysis of multiplicity of infection revealed that msp1 alleles is slightly higher than msp2 with the mean of MOI were 2.69 and 2.27, respectively. Statistical analysis to determine the association between each clinical manifestation and msp1 and msp2 alleles revealed that liver function abnormal value was associated with the msp2 mixed alleles (odds ratio (OR):0.13; 95%CI: 0.03–0.53). Mixed msp1 of K1 + RO33 was associated with severe malaria (OR: 28.50; 95%CI: 1.59–1532.30).

Conclusion
This study found a strong association between severe malaria in Aceh with subjects carrying the msp1 mixed alleles of K1 and RO33. The liver function abnormal value associated with the msp2 mixed allelic subfamilies. Further study in different geographic areas is recommended.