bluuebunny/crossref_metadata_2025_split huggingface dataset:
Towards a values framework for integrated health services: an international Delphi study
Authors: Zonneveld Nick , Raab Jörg , Minkman Mirella M. N. 
Published: March 2020

AbstractBackgroundIn order to organize person-centered health services for a growing number of people with multiple complex health and social care needs, a shift from fragmented to integrated health services delivery has to take place. For the organization of governance in integrated health services, it is important to better understand the underlying factors that drive collaboration, decision-making and behavior between individuals and organizations. Therefore, this article focuses on these underlying normative aspects of integrated health services. This study investigates the values that underpin integrated health services delivery as a concept, by examining the extent to which an initial literature based set of underlying values underpins integrated care and the relevance of these values on the different levels of integration.MethodsAn international Delphi study with 33 experts from 13 different countries was carried out to examine the initial set of underlying values of integrated health services. In addition, the relevance of the values was assessed on the different levels of integration: personal level, professional level, management level and system level.ResultsThe study resulted in a refined set of 18 values of integrated health services developed in three Delphi study rounds. In addition, the results provided insight into the relevance of these values on the personal level (e.g. ‘trustful’), professional level (e.g. ‘collaborative’), management level (e.g. ‘efficient’) and system level (e.g. ‘comprehensive’) of integration. Some of the values score consistent across the different levels of integration while other values score inconsistent across these levels.ConclusionsThe Delphi study resulted in an international normative basis for integrated health services delivery as a concept. The values can be used as ingredients for a values framework and provide a better understanding of the normative aspects of integrated health services delivery. Future research could focus on associated behaviors in practice, the relationship between normative integration and governance, and differences between the value priorities of stakeholder groups.
Utilization of breast cancer screening in Kenya: what are the determinants?
Authors: Antabe Roger , Kansanga Moses , Sano Yujiro , Kyeremeh Emmanuel , Galaa Yvonne 
Published: March 2020

Abstract
Background
Breast cancer accounts for 23% of all cancer cases among women in Kenya. Although breast cancer screening is important, we know little about the factors associated with women’s breast cancer screening utilization in Kenya. Using the Andersen’s behavioural model of health care utilization, we aim to address this void in the literature.

Methods
We draw data on the Kenya Demographic and Health Survey and employ univariate, bivariate, and multivariate analyses.

Results
We find that women’s geographic location, specifically, living in a rural area (OR = 0.89; p < 0.001) and the North Eastern Province is associated with lower odds of women being screened for breast cancer. Moreover, compared to the more educated, richer and insured, women who are less educated, poorer, and uninsured (OR = 0.74; p < 0.001) are less likely to have been screened for breast cancer.

Conclusion
Based on these findings, we recommend place and group-specific education and interventions on increasing breast cancer screening in Kenya.
MiR-33a functions as a tumor suppressor in triple-negative breast cancer by targeting EZH2
Authors: Weihua Zeng , Guorong Zou , Xiaolong Cao , Weizhan Li 
Published: March 2020

Abstract
Background
Increasing reports have confirmed that microRNAs play an important role in breast cancer progression, particularly in triple-negative breast cancer (TNBC). The aim of our study was to investigate the role of miR-33a in TNBC progression.

Methods
PCR assays were performed to detect miR-33a and EZH2 expression in TNBC tissues, adjacent nontumor tissues and cell lines. Western blot, CCK8, Transwell, cell colony formation and EdU cell proliferation, cell cycle analysis and luciferase reporter assays were used to determine the regulation of miR-33a/EZH2 in TNBC progression.

Results
MiR-33a was significantly downregulated in TNBC tissues and cell lines. MiR-33a overexpression in TNBC cells significantly inhibited cell growth and mobility and induced G1 cell cycle arrest. The luciferase reporter assay revealed that EZH2 is a direct target of miR-33a and that it was upregulated in TNBC tissues and cell lines. There was a negative correlation between miR-33a and EZH2 expression in TNBC tissues. EZH2 knockdown exerted similar inhibitory effects, while ectopic expression of EZH2 showed suppressive effects on malignant behaviors induced by miR-33a overexpression in TNBC cells.

Conclusions
These findings revealed that miR-33a is a tumor-suppressive miRNA in TNBC and can inhibit proliferation and mobility and induce G1 cell cycle arrest by directly targeting EZH2.
A geographic identifier assignment algorithm with Bayesian variable selection to identify neighborhood factors associated with emergency department visit disparities for asthma
Authors: Bozigar Matthew , Lawson Andrew , Pearce John , King Kathryn , Svendsen Erik 
Published: March 2020

AbstractBackgroundEcologic health studies often rely on outcomes from health service utilization data that are limited by relatively coarse spatial resolutions and missing geographic information, particularly neighborhood level identifiers. When fine-scale geographic data are missing, the ramifications and strategies for addressing them are not well researched or developed. This study illustrates a novel spatio-temporal framework that combines a geographic identifier assignment (i.e., geographic imputation) algorithm with predictive Bayesian variable selection to identify neighborhood factors associated with disparities in emergency department (ED) visits for asthma.MethodsED visit records with missing fine-scale spatial identifiers (~ 20%) were geocoded using information from known, coarser, misaligned spatial units using an innovative geographic identifier assignment algorithm. We then employed systematic variable selection in a spatio-temporal Bayesian hierarchical model (BHM) predictive framework within the NIMBLE package in R. Our novel methodology is illustrated in an ecologic case study aimed at identifying neighborhood-level predictors of asthma ED visits in South Carolina, United States, from 1999 to 2015. The health outcome was annual ED visit counts in small areas (i.e., census tracts) with primary diagnoses of asthma (ICD9 codes 493.XX) among children ages 5 to 19 years.ResultsWe maintained 96% of ED visit records for this analysis. When the algorithm used areal proportions as probabilities for assignment, which addressed differential missingness of census tract identifiers in rural areas, variable selection consistently identified significant neighborhood-level predictors of asthma ED visit risk including pharmacy proximity, average household size, and carbon monoxide interactions. Contrasted with common solutions of removing geographically incomplete records or scaling up analyses, our methodology identified critical differences in parameters estimated, predictors selected, and inferences. We posit that the differences were attributable to improved data resolution, resulting in greater power and less bias. Importantly, without this methodology, we would have inaccurately identified predictors of risk for asthma ED visits, particularly in rural areas.ConclusionsOur approach innovatively addressed several issues in ecologic health studies, including missing small-area geographic information, multiple correlated neighborhood covariates, and multiscale unmeasured confounding factors. Our methodology could be widely applied to other small-area studies, useful to a range of researchers throughout the world.
The interrupted effect of autophagic flux and lysosomal function induced by graphene oxide in p62-dependent apoptosis of F98 cells
Authors: Zhang Chao , Feng Xiaoli , He Longwen , Zhang Yaqing , Shao Longquan 
Published: March 2020

Abstract
Background
Graphene oxide (GO) nanoparticles (NPs) have been widely applied in various fields, especially in biomedical applications. Extensive studies have suggested that GO can pass through the blood–brain barrier (BBB) and induce abnormal autophagy and cytotoxicity in the central nervous system (CNS). However, the effect and specific mechanism of GO on astrocytes, the most abundant cells in the brain still has not been extensively investigated.

Results
In this study, we systematically explored the toxicity and mechanism of GO exposure in the rat astroglioma-derived F98 cell line using molecular biological techniques (immunofluorescence staining, flow cytometry and Western blot) at the subcellular level and the signaling pathway level. Cells exposed to GO exhibited decreased cell viability and increased lactate dehydrogenase (LDH) release in a concentration- and time-dependent manner. GO-induced autophagy was evidenced by transmission electron microscopy (TEM) and immunofluorescence staining. Western blots showed that LC3II/I and p62 were upregulated and PI3K/Akt/mTOR was downregulated. Detection of lysosomal acidity and cathepsin B activity assay indicated the impairment of lysosomal function. Annexin V-FITC-PI detection showed the occurrence of apoptosis after GO exposure. The decrease in mitochondrial membrane potential (MMP) with an accompanying upregulation of cleaved caspase-3 and Bax/Bcl-2 further suggested that endogenous signaling pathways were involved in GO-induced apoptosis.

Conclusion
The exposure of F98 cells to GO can elicit concentration- and time-dependent toxicological effects. Additionally, increased autophagic response can be triggered after GO treatment and that the blocking of autophagy flux plays a vital role in GO cytotoxicity, which was determined to be related to dysfunction of lysosomal degradation. Importantly, the abnormal accumulation of autophagic substrate p62 protein can induce capase-3-mediated apoptosis. Inhibition of abnormal accumulation of autophagic cargo could alleviate the occurrence of GO-induced apoptosis in F98 cells.
Intravenous delivery of enzalutamide based on high drug loading multifunctional graphene oxide nanoparticles for castration-resistant prostate cancer therapy
Authors: Jiang Wenjun , Chen Jiyuan , Gong Chunai , Wang Yuanyuan , Gao Yuan , Yuan Yongfang 
Published: March 2020

Abstract
Background
Enzalutamide (Enz) has shown limited bioavailability via oral administration. Castration-resistant prostate cancer (CRPC) is frequent among patients receiving 18–24 months of androgen deprivation therapy. The nonsteroidal anti-androgen enzalutamide (Enz) used in the treatment of prostate cancer has shown limited bioavailability via oral administration. Therefore, we developed a multifunctional enzalutamide-loaded graphene oxide nanosystem (TP-GQDss/Enz) for CRPC intravenous treatment, with high drug loading efficiency.

Methods
Aminated graphene quantum dots (GQDs) were first cross-linked via disulfide bonds into a graphene quantum dot derivative of approximately 200 nm (GQDss), which was further functionalized with a tumour-targeting peptide and PEG to form TP-GQDss. Enz was loaded into TP-GQDss for in vitro and in vivo study.

Results
The results showed that high drug-loading efficiency was achieved by TP-GQDss via π–π electron interaction. TP-GQDss could be rapidly internalized by CRPC cells via endocytosis. Moreover, Enz in TP-GQDss could inhibit the growth of C4-2B and LNCaP prostate cancer cell lines in vitro. Further, TP-GQDss exhibited an enhanced cancer-targeting ability and alleviated the side effects of Enz in vivo.

Conclusions
The multifunctional nanocarrier constructed here could accomplish controlled Enz release and serve as an intravenous therapy platform for CRPC.
Cross-cultural adaptation and validation of the Canadian Haemophilia Outcomes-Kids’ Life Assessment Tool (CHO-KLAT) in Côte d’Ivoire (the Ivory Coast)
Authors: Lambert Catherine , Meité N’ Dogomo , Sanogo Ibrahima , Lobet Sébastien , Hermans Cedric , Henrard Séverine , Blanchette Victor , Young Nancy L. 
Published: March 2020

Abstract
Introduction
Health-related quality of life evaluation is recognized as an important outcome in the assessment of boys with haemophilia. In fact, reliable health-related quality of life data are even more critical in developing countries to advocate for government agencies to develop national haemophilia care programmes. However, validated tools are not yet available in sub-Saharan African countries.

Aims
The purpose of this study was to complete the cultural adaptation and validation of the Canadian Haemophilia Outcomes-Kids’ Life Assessment Tool version2.0 (CHO-KLAT2.0) in Côte d’Ivoire.

Methods
The process included four steps: a linguistic adaptation, cognitive debriefing interviews with children and their parents, a validity assessment with the Pediatric Quality of Life Inventory (PedsQL) as a comparator, and a test-retest reliability assessment.

Results
The initial Ivoirian version of the CHO-KLAT2.0 was developed through a linguistic adaptation performed in close collaboration with members of the local medical team and haemophilia community. Cognitive debriefings were completed with five boys and their parents, with the final Ivoirian version of the CHO-KLAT2.0 developed in September 2017. The validation process included 37 boys with haemophilia (mean age: 11.4 years; 34 with severe and three with moderate forms of haemophilia, all treated on demand) and their parents. Among the child-reported population (n = 20), we observed a mean CHO-KLAT2.0 score of 51.3 ± 9.2; there was a moderate correlation between the CHO-KLAT2.0 and PedsQL scores (r = 0.581; p = 0.007) and an inverse correlation of the CHO-KLAT2.0 and PedsQL scores with the global rating of the degree to which the boys were bothered by their haemophilia. The mean parent proxy CHO-KLAT2.0 score (n = 17) was 53.5 ± 9.8. Among the parents, we found no significant correlation between the Ivoirian CHO-KLAT2.0 and PedsQL scores or between the parent-reported scores and the parent global ratings of bother. The test-retest intraclass correlation coefficient was 0.879 (95% CI: 0.673; 0.954) for the child-reported questionnaires and 0.880 (95% CI: 0.694; 0.955) for the proxy-reported questionnaires.

Conclusions
A cross-culturally adapted and validated version of the CHO-KLAT2.0 for Côte d’Ivoire is now available that enables baseline values to be obtained and intervention outcomes (namely, prophylaxis) to be measured in Ivoirian boys with haemophilia.
Explaining breastfeeding experiences and assessing factors affecting breastfeeding self-efficacy in mothers of premature infants: a mixed method study protocol
Authors: Asadi Gholamreza , Aslani Armin , Nayebinia Anvar-Sadat , Fathnezhad-Kazemi Azita 
Published: March 2020

Abstract
Background
Breastfeeding has a great effect on health promotion and disease prevention in premature infants. However, various factors affect the success of breastfeeding process in mothers. The present study aims to: a) explain breastfeeding experiences; b) assess the factors affecting breastfeeding self-efficacy; and c) present a guideline for promoting breastfeeding in mothers of premature infants.

Methods
This mixed-methods study with a sequential explanatory design consisted of three phases. The first phase is qualitative study to explore the breastfeeding experiences in mothers of premature infants. In this phase, the subjects will be selected through purposive sampling; moreover, in-depth individual interviewing will be used for data collection. Finally, the conventional content analysis approach will be employed for data analysis. The second phase is quantitative and will be used a cross-sectional approach to assess the association of the social determinants of health with breastfeeding self-efficacy in mothers of premature infants. In this phase, the multistage cluster sampling method will be used to select 360 subjects who will be visited healthcare centers in Tabriz, Iran. The third phase focused on developing strategies to increase the ability of mothers to breastfeed their premature infants, using the qualitative and quantitative results of previous phases, a review of the related literature, and the nominal group technique will be performed among experts.

Discussion
The present research is the first study that investigated the experiences of breastfeeding and factors influencing breastfeeding self-efficacy in mothers of premature infants. For the purposes of the study, the mixed methods approach will be used which aimed to develop strategies for the improvement of healthcare services in this regard. It is worth noting that there is no strategic guideline in Iran’s healthcare system for the improvement of breastfeeding, especially regarding mothers of premature infants. Therefore, it is hoped that the strategy proposed in the current study can lead to improvements in this regard.

Ethical code
IR.TBZMED.REC.1398.100.
SpikeSegNet-a deep learning approach utilizing encoder-decoder network with hourglass for spike segmentation and counting in wheat plant from visual imaging
Authors: Misra Tanuj , Arora Alka , Marwaha Sudeep , Chinnusamy Viswanathan , Rao Atmakuri Ramakrishna , Jain Rajni , Sahoo Rabi Narayan , Ray Mrinmoy , Kumar Sudhir , Raju Dhandapani , Jha Ranjeet Ranjan , Nigam Aditya , Goel Swati 
Published: March 2020

AbstractBackgroundHigh throughput non-destructive phenotyping is emerging as a significant approach for phenotyping germplasm and breeding populations for the identification of superior donors, elite lines, and QTLs. Detection and counting of spikes, the grain bearing organs of wheat, is critical for phenomics of a large set of germplasm and breeding lines in controlled and field conditions. It is also required for precision agriculture where the application of nitrogen, water, and other inputs at this critical stage is necessary. Further, counting of spikes is an important measure to determine yield. Digital image analysis and machine learning techniques play an essential role in non-destructive plant phenotyping analysis.ResultsIn this study, an approach based on computer vision, particularly object detection, to recognize and count the number of spikes of the wheat plant from the digital images is proposed. For spike identification, a novel deep-learning network, SpikeSegNet, has been developed by combining two proposed feature networks: Local Patch extraction Network (LPNet) and Global Mask refinement Network (GMRNet). In LPNet, the contextual and spatial features are learned at the local patch level. The output of LPNet is a segmented mask image, which is further refined at the global level using GMRNet. Visual (RGB) images of 200 wheat plants were captured using LemnaTec imaging system installed at Nanaji Deshmukh Plant Phenomics Centre, ICAR-IARI, New Delhi. The precision, accuracy, and robustness (F1score) of the proposed approach for spike segmentation are found to be 99.93%, 99.91%, and 99.91%, respectively. For counting the number of spikes, “analyse particles”—function of imageJ was applied on the output image of the proposed SpikeSegNet model. For spike counting, the average precision, accuracy, and robustness are 99%, 95%, and 97%, respectively. SpikeSegNet approach is tested for robustness with illuminated image dataset, and no significant difference is observed in the segmentation performance.ConclusionIn this study, a new approach called as SpikeSegNet has been proposed based on combined digital image analysis and deep learning techniques. A dedicated deep learning approach has been developed to identify and count spikes in the wheat plants. The performance of the approach demonstrates that SpikeSegNet is an effective and robust approach for spike detection and counting. As detection and counting of wheat spikes are closely related to the crop yield, and the proposed approach is also non-destructive, it is a significant step forward in the area of non-destructive and high-throughput phenotyping of wheat.
Correction to: Impact of early intravenous amiodarone administration on neurological outcome in refractory ventricular fibrillation: retrospective analysis of prospectively collected prehospital data
Authors: Lee Dong Keon , Kim Yu Jin , Kim Giwoon , Lee Choung Ah. , Moon Hyung Jun , Oh Jaehoon , Yang Hae Chul , Choi Han Joo , Oh Young Taeck , Park Seung Min 
Published: March 2020

Following the publication of the original article [1], the authors unfortunately became aware of some typesetting and resolution problems in Figs. 1 and 2.
PfSWIB, a potential chromatin regulator for var gene regulation and parasite development in Plasmodium falciparum
Authors: Wang Wei-Feng , Zhang Yi-Long 
Published: March 2020

AbstractBackgroundVarious transcription factors are involved in the process of mutually exclusive expression and clonal variation of thePlasmodiummultigene (var) family. Recent studies revealed that aP. falciparumSWI/SNF-related matrix-associated actin-dependent regulator of chromatin (PfSWIB) might trigger stage-specific programmed cell death (PCD), and was not only crucial for the survival and development of parasite, but also had profound effects on the parasite by interacting with other unknown proteins. However, it remains unclear whetherPfSIWBis involved in transcriptional regulation of this virulence gene and its functional properties.MethodsA conditional knockdown system “PfSWIB-FKBP-LID” was introduced to the parasite clone 3D7, and an integrated parasite line “PfSWIB-HA-FKBP-LID” was obtained by drug cycling and clone screening. Growth curve analysis (GCA) was performed to investigate the growth and development of different parasite lines during 96 hin vitroculturing, by assessing parasitemia. Finally, we performed qPCR assays to detectvargene expression profiling in various comparison groups, as well as the mutually exclusive expression pattern of thevargenes within a single 48 h life-cycle ofP. falciparumin different parasite lines. In addition, RNA-seq was applied to analyze thevargene expression in different lines.ResultsGCA revealed that conditional knockdown ofPfSWIBcould interfere with the growth and development ofP. falciparum. The parasitemia ofPfSWIB∆showed a significant decline at 96 h duringin vitroculture compared with thePfSWIBand 3D7 lines (P < 0.0001). qPCR and RNA-seq analysis confirmed that depletion ofPfSWIBnot only silencesupsA,upsCand partialupsB vargenes, as well as removes the silencing of partialupsB vargenes at the ring stage inPfSWIB∆line, but also leads to aberrant expression ofupsAand partialupsB/upsC vargenes at the mature stage ofP. falciparum, during a single 48-h life-cycle.ConclusionsWe demonstrated thatPfSWIBwas involved in the process of clonal variation invargene expression, and crucial for the survival and development ofPlasmodiumparasite. These findings could provide better understanding of the mechanism and function ofPfSWIBcontributing to the pathogenesis in malaria parasites.