bluuebunny/crossref_metadata_2025_split huggingface dataset:
The small-molecule protein ligand interface stabiliser E7820 induces differential cell line specific responses of integrin α2 expression
Authors: Hülskamp Michael David , Kronenberg Daniel , Stange Richard 
Published: May 2021

Abstract
Background
The mechanism of small-molecule stabilised protein-protein interactions is of growing interest in the pharmacological discovery process. A plethora of different substances including the aromatic sulphonamide E7820 have been identified to act by such a mechanism. The process of E7820 induced CAPERα degradation and the resultant transcriptional down regulation of integrin α2 expression has previously been described for a variety of different cell lines and been made responsible for E7820’s antiangiogenic activity. Currently the application of E7820 in the treatment of various malignancies including pancreas carcinoma and breast cancer is being investigated in pre-clinical and clinical trials. It has been shown, that integrin α2 deficiency has beneficial effects on bone homeostasis in mice. To transfer E7820 treatment to bone-related pathologies, as non-healing fractures, osteoporosis and bone cancer might therefore be beneficial. However, at present no data is available on the effect of E7820 on osseous cells or skeletal malignancies.

Methods
Pre-osteoblastic (MC3T3 and Saos-2) cells and endothelial (eEnd2 cells and HUVECs) cells, each of human and murine origin respectively, were investigated. Vitality assay with different concentrations of E7820 were performed. All consecutive experiments were done at a final concentration of 50 ng/ml E7820. The expression and production of integrin α2 and CAPERα were investigated by quantitative real-time PCR and western blotting. Expression of CAPERα splice forms was differentiated by semi-quantitiative reverse transcriptase PCR.

Results
Here we present the first data showing that E7820 can increase integrin α2 expression in the pre-osteoblast MC3T3 cell line whilst also reproducing canonical E7820 activity in HUVECs. We show that the aberrant activity of E7820 in MC3T3 cells is likely due to differential activity of CAPERα at the integrin α2 promoter, rather than due to differential CAPERα degradation or differential expression of CAPERα spliceforms.

Conclusion
The results presented here indicate that E7820 may not be suitable to treat certain malignancies of musculoskeletal origin, due to the increase in integrin α2 expression it may induce. Further investigation of the differential functioning of CAPERα and the integrin α2 promoter in cells of various origin would however be necessary to more clearly differentiate between cell lines that will positively respond to E7820 from those that will not.
Endodontic length measurements using 3D Endo, cone-beam computed tomography, and electronic apex locator
Authors: Van Pham Khoa 
Published: May 2021

AbstractBackgroundThe objective of this study is to investigate the accuracy of the 3D Endo software, cone-beam computed tomography (CBCT) software, and the electronic apex locator (EAL) in endodontic length determination.Methods302 root canals in 111 human extracted molars were chosen. Access cavity was performed, and root canal lengths were measured with a digital caliper for actual length (AL) and EAL for electronic length. Teeth were then scanned using CBCT device at voxel size of 0.10 mm. It measured root canal lengths using the CBCT (Romexis Viewer), 3D Endo for proposed length (3D-PL) and correct length (3D-CL). Mean differences between the four methods with the AL were calculated and compared. Fisher’s exact test, paired t-test, Bland-Altman plot were used to test the differences among the experimental modalities in working length determination at the significance of 0.05.ResultsThe accuracy in the range of ± 0.5 mm of the EAL ProPex II was highest among the experimental modalities, however this method disagreed with the actual length.ConclusionsThe correct working length after adjustment from the semi-automatically length by the 3D Endo software and Romexis Viewer measurements agreed with the AL.
Current use of the pelvic organ prolapse quantification system in clinical practice among Korean obstetrician-gynecologists
Authors: Kim Soo Rim , Suh Dong Hoon , Jeon Myung Jae 
Published: May 2021

Abstract
Background
To assess current use of the Pelvic Organ Prolapse Quantification (POP-Q) system in clinical practice among Korean obstetrician-gynecologists.

Methods
A web-based questionnaire was sent to 780 Korean Society of Obstetrics and Gynecology members. The items evaluated in the questionnaire were demographic characteristics and current use of the POP-Q system in the evaluation of pelvic organ prolapse (POP) and surgical decision-making. Differences between POP-Q users and nonusers were analyzed by using the two-sample t-test and chi-squared test.

Results
One hundred twenty-six members (16%) responded to the survey. Of the respondents, 48% reported using the POP-Q system in the evaluation of POP. Members who were female, urogynecologists, or performed a high volume of prolapse surgery were more likely to use the POP-Q system (p < 0.05). All but one of the POP-Q users reported using the specific criteria to determine whether each compartmental prolapse should be corrected during prolapse surgery. Most respondents used stage 2 or the hymen as a threshold for prolapse to be corrected for all compartments.

Conclusions
Less than half of Korean obstetrician-gynecologists use the POP-Q system in the evaluation of POP. Almost all of POP-Q users make a surgical decision based on the results of the POP-Q examination.
Prediction of hospital bed capacity during the COVID− 19 pandemic
Authors: Deschepper Mieke , Eeckloo Kristof , Malfait Simon , Benoit Dominique , Callens Steven , Vansteelandt Stijn 
Published: May 2021

Abstract
Background
Prediction of the necessary capacity of beds by ward type (e.g. ICU) is essential for planning purposes during epidemics, such as the COVID− 19 pandemic. The COVID− 19 taskforce within the Ghent University hospital made use of ten-day forecasts on the required number of beds for COVID− 19 patients across different wards.

Methods
The planning tool combined a Poisson model for the number of newly admitted patients on each day with a multistate model for the transitions of admitted patients to the different wards, discharge or death. These models were used to simulate the required capacity of beds by ward type over the next 10 days, along with worst-case and best-case bounds.

Results
Overall, the models resulted in good predictions of the required number of beds across different hospital wards. Short-term predictions were especially accurate as these are less sensitive to sudden changes in number of beds on a given ward (e.g. due to referrals). Code snippets and details on the set-up are provided to guide the reader to apply the planning tool on one’s own hospital data.

Conclusions
We were able to achieve a fast setup of a planning tool useful within the COVID− 19 pandemic, with a fair prediction on the needed capacity by ward type. This methodology can also be applied for other epidemics.
Fostering innovative behavior in health organizations: a PLS-SEM analysis of Norwegian hospital employees
Authors: Mutonyi Barbara Rebecca , Slåtten Terje , Lien Gudbrand 
Published: May 2021

AbstractBackgroundHealth organization research is experiencing a strong refocus on employees’ individual innovative behavior (IIB), revealing that many of the influential factors at work remain uncertain. Hence, this study empirically examines fostering of hospital employees’ IIB by focusing on direct and indirect relationships of organizational culture (here labeledinternal market-oriented culture, IMOC), psychological capital (PsyCap), and organizational commitment (OC).MethodsThe study focused on a sample of 1008 hospital employees, using a partial least squares–structural equation modeling method to analyze and test the relationships hypothesized in this study. A multigroup comparison was performed to test the heterogeneity of personal characteristics. The indirect relationships of PsyCap were tested using mediator analyses.ResultsOur results reveal that IMOC has a positive and significant correlation to employees’ PsyCap and IIB. PsyCap is directly related to IIB and indirectly related to IMOC and IIB. Furthermore, the study found that IIB is related to OC.ConclusionsThis study extends the current debate on how IIB is fostered at work by examining PsyCap and IMOC as antecedents of IIB. The study has added to the IIB research area by examining the role of IIB on OC. The study is among the first attempts in its category to contribute to health organizations and managers by empirically examining the role of IMOC on employees’ PsyCap and IIB—and, in turn, their OC.
Evaluation of a serum-based antigen test for tuberculosis in HIV-exposed infants: a diagnostic accuracy study
Authors: Mao Liyan , LaCourse Sylvia M. , Kim Soyeon , Liu Chang , Ning Bo , Bao Duran , Fan Jia , Lyon Christopher J. , Sun Ziyong , Nachman Sharon , Mitchell Charles D. , Hu Tony Y. 
Published: May 2021

Abstract
Background
Non-sputum methods are urgently needed to improve tuberculosis diagnosis and treatment monitoring in children. This study evaluated the ability of a serum assay quantifying a species-specific peptide of the Mycobacterium tuberculosis CFP-10 virulence factor via nanotechnology and matrix-assisted laser desorption ionization time-of-flight mass spectrometry to diagnose tuberculosis in HIV-infected and HIV-uninfected infants.

Methods
Serum CFP-10 peptide signal was blinded evaluated in cryopreserved sera of 519 BCG-immunized, HIV-exposed infants (284 HIV-infected, 235 HIV-uninfected) from a multi-center randomized placebo-controlled isoniazid prophylaxis trial conducted in southern Africa between 2004 and 2008, who were followed up to 192 weeks for Mtb infection and TB. Children were classified as confirmed, unconfirmed, or unlikely tuberculosis cases using 2015 NIH diagnostic criteria for pediatric TB.

Results
In HIV-infected infants, CFP-10 signal had 100% sensitivity for confirmed TB (5/5, 95% CI, 47.8–100) and 83.7% sensitivity for unconfirmed TB (36/43, 95% CI 69.3–93.2), with 93.1% specificity (203/218, 95% CI 88.9–96.1). In HIV-uninfected infants, CFP-10 signal detected the single confirmed TB case and 75.0% of unconfirmed TB cases (15/20; 95% CI 50.9–91.3), with 96.2% specificity (177/184, 95% CI, 92.3–98.5). Serum CFP-10 achieved 77% diagnostic sensitivity for confirmed and unconfirmed TB (13/17, 95% CI, 50–93%) at ≤ 24 weeks pre-diagnosis, and both CFP-10-positivity and concentration declined following anti-TB therapy initiation.

Conclusions
Serum CFP-10 signal exhibited high diagnostic sensitivity and specificity for tuberculosis in HIV-infected and HIV-uninfected infants and potential utility for early TB detection and monitoring of anti-TB treatment responses.
Signature RNAS and related regulatory roles in type 1 diabetes mellitus based on competing endogenous RNA regulatory network analysis
Authors: Shi Qinghong , Yao Hanxin 
Published: May 2021

Abstract
Background
Our study aimed to investigate signature RNAs and their potential roles in type 1 diabetes mellitus (T1DM) using a competing endogenous RNA regulatory network analysis.

Methods
Expression profiles of GSE55100, deposited from peripheral blood mononuclear cells of 12 T1DM patients and 10 normal controls, were downloaded from the Gene Expression Omnibus to uncover differentially expressed long non-coding RNAs (lncRNAs), mRNAs, and microRNAs (miRNAs). The ceRNA regulatory network was constructed, then functional and pathway enrichment analysis was conducted. AT1DM-related ceRNA regulatory network was established based on the Human microRNA Disease Database to carry out pathway enrichment analysis. Meanwhile, the T1DM-related pathways were retrieved from the Comparative Toxicogenomics Database (CTD).

Results
In total, 847 mRNAs, 41 lncRNAs, and 38 miRNAs were significantly differentially expressed. The ceRNA regulatory network consisted of 12 lncRNAs, 10 miRNAs, and 24 mRNAs. Two miRNAs (hsa-miR-181a and hsa-miR-1275) were screened as T1DM-related miRNAs to build the T1DM-related ceRNA regulatory network, in which genes were considerably enriched in seven pathways. Moreover, three overlapping pathways, including the phosphatidylinositol signaling system (involving PIP4K2A, INPP4A, PIP4K2C, and CALM1); dopaminergic synapse (involving CALM1 and PPP2R5C); and the insulin signaling pathway (involving CBLB and CALM1) were revealed by comparing with T1DM-related pathways in the CTD, which involved four lncRNAs (LINC01278, TRG-AS1, MIAT, and GAS5-AS1).

Conclusion
The identified signature RNAs may serve as important regulators in the pathogenesis of T1DM.
SCUBE3 serves as an independent poor prognostic factor in breast cancer
Authors: Huo Qin , He Xi , Li Zhenwei , Yang Fan , He Shengnan , Shao Ling , Hu Ye , Chen Siqi , Xie Ni 
Published: May 2021

Abstract
Background
Accumulating evidences indicate that the signal peptide-CUB-EGF-like domain-containing protein 3 (SCUBE3) plays a key role in the development and progression of many human cancers. However, the underlying mechanism and prognosis value of SCUBE3 in breast cancer are still unclear.

Methods
The clinical data of 137 patients with breast cancer who underwent surgical resection in Taizhou Hospital of Zhejiang Province were retrospectively analyzed. We first conducted a comprehensive study on the expression pattern of SCUBE3 using the Tumor Immune Estimation Resource (TIMER) and UALCAN databases. In addition, the expression of SCUBE3 in breast tumor tissues was confirmed by immunohistochemistry. The protein–protein interaction analysis and functional enrichment analysis of SCUBE3 were analyzed using the STRING and Enrichr databases. Moreover, tissue microarray (TMA) was used to analyze the relationship between SCUBE3 expression levels and clinical-pathological parameters, such as histological type, grade, the status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2). We further supplemented and identified the above results using the UALCAN and bc-GenExMiner v4.4 databases from TCGA data. The correlation between the expression of SCUBE3 and survival was calculated by multivariate Cox regression analysis to investigate whether SCUBE3 expression may be an independent prognostic factor of breast cancer.

Results
We found that the expression level of SCUBE3 was significantly upregulated in breast cancer tissue compared with adjacent normal tissues. The results showed that the distribution of breast cancer patients in the high expression group and the low expression group was significantly different in ER, PR, HER2, E-cadherin, and survival state (p < 0.05), but there was no significant difference in histologic grade, histologic type, tumor size, lymph node metastasis, TMN stage, subtypes, or recurrence (p > 0.05). In addition, the high expression of SCUBE3 was associated with relatively poor prognosis of ER- (p = 0.012), PR- (p = 0.029), HER2 + (p = 0.007). The multivariate Cox regression analysis showed that the hazard ratio (HR) was 2.80 (95% CI 1.20–6.51, p = 0.0168) in individuals with high SCUBE3 expression, and HR was increased by 1.86 (95% CI 1.06–3.25, p = 0.0300) for per 1-point increase of SCUBE3 expression.

Conclusions
These findings demonstrate that the high expression of SCUBE3 indicates poor prognosis in breast cancer. SCUBE3 expression may serve as a potential diagnostic indicator of breast cancer.
Application of an ultrasound semi-quantitative assessment in the degradation of silk fibroin scaffolds in vivo
Authors: Cai Lihui , Gao Nan , Sun TingYu , Bi Ke , Chen Xin , Zhao Xia 
Published: May 2021

Abstract
Background
Research on the degradation of silk fibroin (SF) scaffolds in vivo lacks uniform and effective standards and experimental evaluation methods. This study aims to evaluate the application of ultrasound in assessing the degradation of SF scaffolds.

Methods
Two groups of three-dimensional regenerated SF scaffolds (3D RSFs) were implanted subcutaneously into the backs of Sprague-Dawley rats. B-mode ultrasound and hematoxylin and eosin (HE) staining were performed on days 3, 7, 14, 28, 56, 84, 112, 140, and 196. The cross-sectional areas for two groups of 3D RSFs that were obtained using these methods were semi-quantitatively analyzed and compared to evaluate the biodegradation of the implanted RSFs.

Results
The 3D RSFs in the SF-A group were wholly degraded at the 28th week after implantation. In contrast, the 3D RSFs in the SF-B group were completely degraded at the 16th week. Ultrasonic examination showed that the echoes of 3D RSFs in both groups gradually decreased with the increase of the implantation time. In the early stages of degradation, the echoes of the samples were higher than the echo of the muscle. In the middle of degeneration, the echoes were equal to the echo of the muscle. In the later stage, the echoes of the samples were lower than that of the muscle. The above changes in the SF-B group were earlier than those in the SF-A group. Semi-quantitative analysis of the cross-sectional areas detected using B-mode ultrasound revealed that the degradations of the two 3D RSF groups were significantly different. The degradation rate of the SF-B group was found to be higher than that of the SF-A group. This was consistent with the semi-quantitative detection results for HE staining. Regression analysis showed that the results of the B-mode ultrasound and HE staining were correlated in both groups, indicating that B-mode ultrasound is a reliable method to evaluate the SF scaffold degradation in vivo.

Conclusions
This study suggests that B-mode ultrasound can clearly display the implanted SF scaffolds non-invasively and monitor the degradation of the different SF scaffolds after implantation in living organisms in real-time.
Infection, dissemination, and transmission efficiencies of Zika virus in Aedes aegypti after serial passage in mosquito or mammalian cell lines or alternating passage in both cell types
Authors: Talavera-Aguilar Lourdes G. , Murrieta Reyes A. , Kiem Sungmin , Cetina-Trejo Rosa C. , Baak-Baak Carlos M. , Ebel Gregory D. , Blitvich Bradley J. , Machain-Williams Carlos 
Published: May 2021

Abstract
Background
Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) with an urban transmission cycle that primarily involves humans and Aedes aegypti. Evidence suggests that the evolution of some arboviruses is constrained by their dependency on alternating between disparate (vertebrate and invertebrate) hosts. The goals of this study are to compare the genetic changes that occur in ZIKV after serial passaging in mosquito or vertebrate cell lines or alternate passaging in both cell types and to compare the replication, dissemination, and transmission efficiencies of the cell culture-derived viruses in Ae. aegypti.

Methods
An isolate of ZIKV originally acquired from a febrile patient in Yucatan, Mexico, was serially passaged six times in African green monkey kidney (Vero) cells or Aedes albopictus (C6/36) cells or both cell types by alternating passage. A colony of Ae. aegypti from Yucatan was established, and mosquitoes were challenged with the cell-adapted viruses. Midguts, Malpighian tubules, ovaries, salivary glands, wings/legs and saliva were collected at various times after challenge and tested for evidence of virus infection.

Results
Genome sequencing revealed the presence of two non-synonymous substitutions in the premembrane and NS1 regions of the mosquito cell-adapted virus and two non-synonymous substitutions in the capsid and NS2A regions of both the vertebrate cell-adapted and alternate-passaged viruses. Additional genetic changes were identified by intrahost variant frequency analysis. Virus maintained by continuous C6/36 cell passage was significantly more infectious in Ae. aegypti than viruses maintained by alternating passage and consecutive Vero cell passage.

Conclusions
Mosquito cell-adapted ZIKV displayed greater in vivo fitness in Ae. aegypti compared to the other viruses, indicating that obligate cycling between disparate hosts carries a fitness cost. These data increase our understanding of the factors that drive ZIKV adaptation and evolution and underscore the important need to consider the in vivo passage histories of flaviviruses to be evaluated in vector competence studies.

Graphical abstract
The prevalence of the iutA and ibeA genes in Escherichia coli isolates from severe and non-severe patients with bacteremic acute biliary tract infection is significantly different
Authors: Ikeda Mahoko , Kobayashi Tatsuya , Fujimoto Fumie , Okada Yuta , Higurashi Yoshimi , Tatsuno Keita , Okugawa Shu , Moriya Kyoji 
Published: May 2021

Abstract
Background
Although Escherichia coli is the most frequently isolated microorganism in acute biliary tract infections with bacteremia, data regarding its virulence are limited.

Results
Information on cases of bacteremia in acute biliary tract infection in a retrospective study was collected from 2013 to 2015 at a tertiary care hospital in Japan. Factors related to the severity of infection were investigated, including patient background, phylogenetic typing, and virulence factors of E. coli, such as adhesion, invasion, toxins, and iron acquisition.
In total, 72 E. coli strains were identified in 71 cases, most of which primarily belonged to the B2 phylogroup (68.1%). The presence of the iutA gene (77.3% in the non-severe group, 46.4% in the severe group, P = 0.011) and the ibeA gene (9.1% in the non-severe group, and 35.7% in the severe group, P = 0.012) was significantly associated with the severity of infection. Among the patient characteristics, diabetes mellitus with organ involvement and alkaline phosphatase were different in the severe and non-severe groups.

Conclusions
We showed that bacteremic E. coli strains from acute biliary tract infections belonged to the virulent (B2) phylogroup. The prevalence of the iutA and ibeA genes between the two groups of bacteremia severity was significantly different.
Research on Whole-Process Tensile Behavior of Headed Studs in Steel–Concrete Composite Structures
Authors: Zhuang Liang-Dong , Chen Hong-Bing , Ma Yuan , Ding Ran 
Published: May 2021

AbstractThe headed studs have been widely applied in steel–concrete composite structures as shear connectors. However, the tensile performance of headed studs is also key to the structural performance in many cases such as the semi-rigid composite joints including steel beam–concrete wall joint and steel column–base joint. Therefore, this study presents experimental and analytical study on the whole-process tensile behavior of headed studs. Tests on a total of 33 pullout specimens are first conducted. The tensile capacity and load–deformation behavior of the anchorage concrete, which dominates the structural performance of headed studs, are thoroughly analyzed. In addition, test data in the literature are collected for quantitatively evaluating the influence of embedment depth, bearing area, boundary conditions, and concrete strength on the tensile behavior of the anchorage concrete. On the basis of the influence evaluation, an analytical model represented by a piecewise function is proposed to describe the whole-process load–deformation behavior of the anchorage concrete and validated through the comparison between the predicted curves and all collected experimental results. Then the proposed model is applied to simulate the rotational behavior of the typical semi-rigid joint anchored by headed studs, which takes the contribution of the anchorage concrete into consideration, and is verified by experimental results. The research findings indicate that tensile behavior of anchorage concrete is crucial to the structural performance of semi-rigid joints, even for headed studs with large embedment depth and bearing area.