bluuebunny/crossref_metadata_2025_split huggingface dataset:
Percutaneous administration of allogeneic bone-forming cells for the treatment of delayed unions of fractures: a pilot study
Authors: Jayankura Marc , Schulz Arndt Peter , Delahaut Olivier , Witvrouw Richard , Seefried Lothar , Berg Bruno Vande , Heynen Guy , Sonnet Wendy 
Published: June 2021

Abstract
Background
Overall, 5–10% of fractures result in delayed unions or non-unions, causing major disabilities and a huge socioeconomic burden. Since rescue surgery with autologous bone grafts can cause additional challenges, alternative treatment options have been developed to stimulate a deficient healing process. This study assessed the technical feasibility, safety and preliminary efficacy of local percutaneous implantation of allogeneic bone-forming cells in delayed unions of long bone fractures.

Methods
In this phase I/IIA open-label pilot trial, 22 adult patients with non-infected delayed unions of long bone fractures, which failed to consolidate after 3 to 7 months, received a percutaneous implantation of allogeneic bone-forming cells derived from bone marrow mesenchymal stem cells (ALLOB; Bone Therapeutics) into the fracture site (50 × 106 to 100 × 106 cells). Patients were monitored for adverse events and need for rescue surgery for 30 months. Fracture healing was monitored by Tomographic Union Score (TUS) and modified Radiographic Union Score. The health status was evaluated using the Global Disease Evaluation (GDE) score and pain at palpation using a visual analogue scale. The presence of reactive anti-human leukocyte antigen (HLA) antibodies was evaluated.

Results
During the 6-month follow-up, three serious treatment-emergent adverse events were reported in two patients, of which two were considered as possibly treatment-related. None of the 21 patients in the per-protocol efficacy population needed rescue surgery within 6 months, but 2/21 (9.5%) patients had rescue surgery within 30 months post-treatment. At 6 months post-treatment, an improvement of at least 2 points in TUS was reached in 76.2% of patients, the GDE score improved by a mean of 48%, and pain at palpation at the fracture site was reduced by an average of 61% compared to baseline. The proportion of blood samples containing donor-specific anti-HLA antibodies increased from 8/22 (36.4%) before treatment to 13/22 (59.1%) at 6 months post-treatment, but no treatment-mediated allogeneic immune reactions were observed.

Conclusion
This pilot study showed that the percutaneous implantation of allogeneic bone-forming cells was technically feasible and well tolerated in patients with delayed unions of long bone fractures. Preliminary efficacy evidence is supporting the further development of this treatment.

Trial registration
NCT02020590. Registered on 25 December 2013. ALLOB-DU1, A pilot Phase I/IIa, multicentre, open proof-of-concept study on the efficacy and safetyof allogeneic osteoblastic cells (ALLOB®) implantation in non-infected delayed-union fractures.
Bone marrow-derived mesenchymal stem/stromal cells in patients with acute myeloid leukemia reveal transcriptome alterations and deficiency in cellular vitality
Authors: Zhang Leisheng , Chi Ying , Wei Yimeng , Zhang Wenxia , Wang Fuxu , Zhang Lei , Zou Linglin , Song Baoquan , Zhao Xing , Han Zhongchao 
Published: June 2021

Abstract
Background
State-of-the-art advances have indicated the pivotal characteristics of bone marrow-derived mesenchymal stem/stromal cells (BM-MSCs) in hematopoietic microenvironment as well as coordinate contribution to hematological malignancies. However, the panoramic view and detailed dissection of BM-MSCs in patients with acute myeloid leukemia (AML-MSCs) remain obscure.

Methods
For the purpose, we isolated and identified AML-MSCs together with healthy donor-derived HD-MSCs from the bone marrow mononuclear cells (BM-MNCs) by using the standard density gradient centrifugation based on clinical diagnosis and cellular phenotypic analysis. Subsequently, we systematically compared the potential similarities and discrepancy both at the cellular and molecular levels via flow cytometry, multilineage differentiation, chromosome karyotyping, cytokine quantification, and transcriptome sequencing and bioinformatic analysis including single-nucleotide polymorphism (SNP), gene ontology (GO), HeatMap, principal component analysis (PCA), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA).

Results
On the one hand, AML-MSCs exhibited undistinguishable signatures in cytomorphology, surface biomarker expression pattern, stemness, chromosome karyotype, and chondrogenesis as HD-MSCs, whereas with impaired adipogenesis, enhanced osteogenesis, and variations in cytokine expression pattern. On the other hand, with the aid of genomic and bioinformatic analyses, we verified that AML-MSCs displayed multidimensional discrepancy with HD-MSCs both in genome-wide gene expression profiling and genetic variation spectrum. Simultaneously, the deficiency of cellular vitality including proliferation and apoptosis in AML-MSCs was largely rescued by JAK-STAT signaling inhibition.

Conclusions
Overall, our findings elucidated that AML-MSCs manifested multifaceted alterations in biological signatures and molecular genetics, and in particular, the deficiency of cellular vitality ascribed to over-activation of JAK-STAT signal, which collectively provided systematic and overwhelming new evidence for decoding the pathogenesis of AML and exploring therapeutic strategies in future.
Pattern formation in a 2-population homogenized neuronal network model
Authors: Kolodina Karina , Wyller John , Oleynik Anna , Sørensen Mads Peter 
Published: June 2021

AbstractWe study pattern formation in a 2-population homogenized neural field model of the Hopfield type in one spatial dimension with periodic microstructure. The connectivity functions are periodically modulated in both the synaptic footprint and in the spatial scale. It is shown that the nonlocal synaptic interactions promote a finite band width instability. The stability method relies on a sequence of wave-number dependent invariants of$2\times 2$2×2-stability matrices representing the sequence of Fourier-transformed linearized evolution equations for the perturbation imposed on the homogeneous background. The generic picture of the instability structure consists of a finite set of well-separated gain bands. In the shallow firing rate regime the nonlinear development of the instability is determined by means of the translational invariant model with connectivity kernels replaced with the corresponding period averaged connectivity functions. In the steep firing rate regime the pattern formation process depends sensitively on the spatial localization of the connectivity kernels: For strongly localized kernels this process is determined by the translational invariant model with period averaged connectivity kernels, whereas in the complementary regime of weak and moderate localization requires the homogenized model as a starting point for the analysis. We follow the development of the instability numerically into the nonlinear regime for both steep and shallow firing rate functions when the connectivity kernels are modeled by means of an exponentially decaying function. We also study the pattern forming process numerically as a function of the heterogeneity parameters in four different regimes ranging from the weakly modulated case to the strongly heterogeneous case. For the weakly modulated regime, we observe that stable spatial oscillations are formed in the steep firing rate regime, whereas we get spatiotemporal oscillations in the shallow regime of the firing rate functions.
Economic burden of lung cancer in Turkey: a cost of illness study from payer perspective
Authors: Cicin Irfan , Oksuz Ergun , Karadurmus Nuri , Malhan Simten , Gumus Mahmut , Yilmaz Ulku , Cansever Levent , Cinarka Halit , Cetinkaya Erdogan , Kiyik Murat , Ozet Ahmet ,   Lung Cancer Report Study Group Turkey, Cicin Irfan , Oksuz Ergun , Karadurmus Nuri , Malhan Simten , Gumus Mahmut , Yilmaz Ulku , Cansever Levent , Cinarka Halit , Cetinkaya Erdogan , Kiyik Murat , Ozet Ahmet ,   on behalf of the Turkish Society of Lung Cancer,   Lung Health and Intensive Care Association,   University of Health Sciences,   Turkish Society of Medical Oncology,   National Cancer Institute,   Turkish Respiratory Society
Published: June 2021

Abstract
Background
This study was designed to estimate economic burden of lung cancer in Turkey from payer perspective based on expert panel opinion on practice patterns in clinical practice.

Methods
In this cost of illness study, direct medical cost was calculated based on cost items related to outpatient visits, laboratory and radiological tests, hospitalizations/interventions, drug treatment, adverse events and metastasis. Indirect cost was calculated based on lost productivity due to early retirement, morbidity and premature death resulting from the illness, the value of lost productivity due to time spent by family caregivers and cost of formal caregivers.

Results
Cost analysis revealed the total per patient annual direct medical cost for small cell lung cancer to be €8772), for non-small-cell lung cancer to be €10,167. Total annual direct medical cost was €497.9 million, total annual indirect medical cost was €1.1 billion and total economic burden of lung cancer was €1.6 billion. Hospitalization/interventions (41%) and indirect costs (68.6%) were the major cost drivers for total direct costs and the overall economic burden of lung cancer, respectively.

Conclusions
Our findings indicate per patient direct medical costs of small cell lung cancer and non-small-cell lung cancer to be substantial and comparable, indicating the substantial economic burden of lung cancer in terms of both direct and indirect costs. Our findings indicate that hospitalization/interventions cost item and indirect costs were the major cost drivers for total direct costs and the overall economic burden of lung cancer, respectively. Our findings emphasize the potential role of improved cancer prevention and early diagnosis strategies, by enabling cost savings related to drug treatment and metastasis management cost items, in sustainability of cancer treatments.
An image denoising method based on BP neural network optimized by improved whale optimization algorithm
Authors: Wang Chunzhi , Li Min , Wang Ruoxi , Yu Han , Wang Shuping 
Published: June 2021

AbstractAs an important part of smart city construction, traffic image denoising has been studied widely. Image denoising technique can enhance the performance of segmentation and recognition model and improve the accuracy of segmentation and recognition results. However, due to the different types of noise and the degree of noise pollution, the traditional image denoising methods generally have some problems, such as blurred edges and details, loss of image information. This paper presents an image denoising method based on BP neural network optimized by improved whale optimization algorithm. Firstly, the nonlinear convergence factor and adaptive weight coefficient are introduced into the algorithm to improve the optimization ability and convergence characteristics of the standard whale optimization algorithm. Then, the improved whale optimization algorithm is used to optimize the initial weight and threshold value of BP neural network to overcome the dependence in the construction process, and shorten the training time of the neural network. Finally, the optimized BP neural network is applied to benchmark image denoising and traffic image denoising. The experimental results show that compared with the traditional denoising methods such as Median filtering, Neighborhood average filtering and Wiener filtering, the proposed method has better performance in peak signal-to-noise ratio.
A four-quadrant mobility model-based routing protocol for post-earthquake emergency communication network
Authors: Wang Xiaoming , Guo Chang 
Published: June 2021

AbstractEmergency communication network (ECN) is the important infrastructure to acquire the real-time information after disaster, which is essential for rescue task. However, the existed routing protocols seldom consider the uneven distribution of rescue area so that cannot satisfy the ECN’s requirement and the quality of rescue needs improvement. In this paper, we avoided the traditional linear propulsion from rim to core and proposed a novel four-quadrant mobility model (FQMM), which makes rescuers arrive the most intensity core area first, which can improve the rescue quality. Then, a FQMM-based protocol (FQMMBP) for ECN is designed, which aims to improve the performance of ECN in terms of package delivery rate (PDR) and end-to-end delay. Finally, we set up a virtual earthquake scenario to simulate our proposed protocol in NS2. Results show that the proposed protocol outperforms to the three compared routing protocols, i.e., AODV, DSDV and DSR. The average FDR is improved by 16.31%, and the average reduction of delay is 64.45%, which shows our proposed scheme’s advantages in quality of rescue.
Therapeutic potential of pluripotent stem cell-derived dopaminergic progenitors in Parkinson’s disease: a systematic review protocol
Authors: Karimi Aliasghar , Elmi Mitra , Shiri Zahra , Baharvand Hossein 
Published: June 2021

Abstract
Background
Parkinson’s disease (PD) is the second most common age-dependent neurodegenerative disease that causes motor and cognitive disabilities. This disease is associated with a loss of dopamine content within the putamen, which stems from the degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). Several approved drugs are available that can effectively treat symptoms of PD. However, long-term medical management is often complicated and does not delay or halt disease progression. Alternatively, cell replacement strategies can address these shortcomings and provide dopamine where it is needed. Although using human pluripotent stem cells (hPSCs) for treatment of PD is a promising alternative, no consensus in the literature pertains to efficacy concerns of hPSC-based therapy for PD. This systematic review aims to investigate the efficacy of primate PSC-derived DA progenitor transplantation to treat PD in preclinical studies.

Methods
This is a systematic review of preclinical studies in animal models of PD. We intend to use the following databases as article sources: MEDLINE (via PubMed), Web of Science, and SCOPUS without any restrictions on language or publication status for all related articles published until the end of April 2021. Two independent reviewers will select the titles and abstracts, extract data from qualifying studies, and assess the risk of bias using the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) risk of bias tool and the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies (CAMARADES) checklist. Apomorphine-induced rotation test (APO-IR) and amphetamine-induced rotation test (AMP-IR) are defined as the primary outcomes. The standardized mean difference (SMD) by Hedges’ g method (r) and odds ratio (OR) and related 95% confidence interval (CI) will be calculated to determine the size effect of the treatment. The heterogeneity between studies will be calculated by “I2 inconsistency of values and Cochran’s Q statistical test,” where I2 > 50% and/or p < 0.10 suggests high heterogeneity. Meta-analyses of random effects will be run when appropriate.

Discussion
This study will present an overview of preclinical research on PSCs and their therapeutic effects in PD animal models. This systematic review will point out the strengths and limitations of studies in the current literature while encouraging the funding of new studies by public health managers and governmental bodies.
Application of weighting methods for presenting risk-of-bias assessments in systematic reviews of diagnostic test accuracy studies
Authors: Vali Yasaman , Leeflang Mariska M. G. , Bossuyt Patrick M. M. 
Published: June 2021

AbstractBackgroundAn assessment of the validity of individual diagnostic accuracy studies in systematic reviews is necessary to guide the analysis and the interpretation of results. Such an assessment is performed for each included study and typically reported at the study level. As studies may differ in sample size and disease prevalence, with larger studies contributing more to the meta-analysis, such a study-level report does not always reflect the risk of bias in the total body of evidence. We aimed to develop improved methods of presenting the risk of bias in the available evidence on diagnostic accuracy of medical tests in systematic reviews, reflecting the relative contribution of the study to the body of evidence in the review.MethodsWe applied alternative methods to represent evaluations with the Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2), weighting studies according to their relative contribution to the total sample size or their relative effective sample size. We used these methods in four existing systematic reviews of diagnostic accuracy studies, including 9, 13, 22, and 32 studies, respectively.ResultsThe risk-of-bias summaries for each domain of the QUADAS-2 checklist changed in all four sets of studies after replacing unit weights for the studies with relative sample sizes or with the relative effective sample size. As an example, the risk of bias was high in the patient selection domain in 31% of the studies in one review, unclear in 23% and low in 46% of studies. Weighting studies according to the relative sample size changed the corresponding proportions to 4%, 4%, and 92%, respectively. The difference between the two weighting methods was small and more noticeable when the reviews included a smaller number of studies with wider range of sample size.ConclusionsWe present an alternative way of presenting the results of risk-of-bias assessments in systematic reviews of diagnostic accuracy studies. Weighting studies according to their relative sample size or their relative effective sample size can be used as more informative summaries of the risk of bias in the total body of available evidence.Systematic review registrationsNot applicable
A scoping review of researchers’ involvement in health policy dialogue in Africa
Authors: Yimgang Doris , Danhoundo Georges , Kusi-Appiah Elizabeth , Sunder Vijit , Campbell Sandra , Yaya Sanni 
Published: June 2021

AbstractBackgroundImproving evidence-informed policy dialogue to support the development and implementation of national health policies is vital, but there is limited evidence on researchers’ roles in policy dialogue processes in Africa. The objective of this study is to examine researchers’ involvement in health policy dialogue in Africa.MethodsThe database search of this scoping review was conducted from inception to January 24, 2021, by an expert searcher/librarian to determine the extent of evidence, barriers, and facilitators of researchers’ involvement in health policy dialogues in Africa. PROSPERO, Wiley Cochrane Library, OVID Medline, OVID EMBASE, OVID PsycINFO, OVID Global Health, EBSCO CINAHL, BASE (Bielefeld Academic Search Engine), and Google/Google Scholar were searched using key words representing the concepts “policy dialogue”, “health”, and “Africa”. No limits were applied. A narrative summary of results was presented.ResultsThere were 26 eligible studies representing 21 African countries. Significant discrepancies in researchers’ involvement existed across countries. In 62% of the countries, there was suboptimal involvement of researchers in policy dialogues due to no or partial participation in policy dialogues. Major barriers included limited funding, lack of evidence in the public health field of interest, and skepticism of policymakers. The presence of an interface for exchange, demand for scientific evidence, and donors’ funding were the most reported facilitators.ConclusionsTo improve the uptake of evidence in health policy-making processes, an environment of trust and communication between policymakers and researchers must be established. Policymakers need to demonstrate that they value research, by providing adequate funding, promoting knowledge translation activities, and supporting personal and professional development opportunities for researchers.
Iterative algorithms of common solutions for a hierarchical fixed point problem, a system of variational inequalities, and a split equilibrium problem in Hilbert spaces
Authors: Zhao Yali , Liu Xin , Sun Ruonan 
Published: June 2021

AbstractIn this paper, we suggest and analyze an iterative algorithm to approximate a common solution of a hierarchical fixed point problem for nonexpansive mappings, a system of variational inequalities, and a split equilibrium problem in Hilbert spaces. Under some suitable conditions imposed on the sequences of parameters, we prove that the sequence generated by the proposed iterative method converges strongly to a common element of the solution set of these three kinds of problems. The results obtained here extend and improve the corresponding results of the relevant literature.
Positive solutions of a second-order nonlinear Robin problem involving the first-order derivative
Authors: Yang Zhilin 
Published: June 2021

AbstractThis paper is concerned with the second-order nonlinear Robin problem involving the first-order derivative:
$$ \textstyle\begin{cases} u''+f(t,u,u^{\prime })=0, \\ u(0)=u'(1)-\alpha u(1)=0,\end{cases} $$

{

u
″

+
f
(
t
,
u
,

u
′

)
=
0
,

u
(
0
)
=

u
′

(
1
)
−
α
u
(
1
)
=
0
,

where $f\in C([0,1]\times \mathbb{R}^{2}_{+},\mathbb{R}_{+})$
f
∈
C
(
[
0
,
1
]
×

R
+
2

,

R
+

)
and $\alpha \in ]0,1[$
α
∈
]
0
,
1
[
. Based on a priori estimates, we use fixed point index theory to establish some results on existence, multiplicity and uniqueness of positive solutions thereof, with the unique positive solution being the limit of of an iterative sequence. The results presented here generalize and extend the corresponding ones for nonlinearities independent of the first-order derivative.
Blood lead and cadmium levels are negatively associated with bone mineral density in young female adults
Authors: Lu Jianfeng , Lan Ji , Li Xiao’e , Zhu Zhongxin 
Published: June 2021

Abstract
Background
The organ toxicities of lead and cadmium have been extensively studied; however, studies of their toxic effects on bone remain limited, especially in young adults. The objective of this study was to examine the associations of blood lead levels (BLL) and blood cadmium levels (BCL) with bone mineral density (BMD) among young adults.

Methods
We performed a cross-sectional study using the National Health and Nutrition Examination Survey 2011–2018 database. Because of the skewed distribution, BLL and BCL were Ln-transformed for analysis. Weighted multivariate regressions were performed to evaluate the associations between LnBLL and LnBCL and lumbar BMD. Subgroup analyses were further performed.

Results
A total of 3234 participants aged 20–35 years were included in this study. No significant association between LnBLL and lumbar BMD was found (β = − 5.6, 95%CI: − 13.5–2.3). However, in the subgroup analysis stratified by sex, this association became negative in women (β = − 18.2, 95%CI: − 29.9– − 6.4). Moreover, this negative association was more prominent in female blacks (β = − 35.5, 95%CI: − 63.4– − 7.6). On the other hand, a negative association between LnBCL and lumbar BMD was found (β = − 7.4, 95%CI: − 14.0– − 0.8). In the subgroup analysis stratified by sex, this negative association only existed in women (β = − 18.7, 95%CI: − 28.0– − 9.5). Moreover, this negative association was more prominent in female whites (β = − 31.1, 95%CI: − 46.2– − 16.1).

Conclusions
Our finding showed that both BLL and BCL were independently and negatively associated with lumbar BMD among young females, but not among young males.