bluuebunny/crossref_metadata_2025_split huggingface dataset:
Topical and intravenous administration of human umbilical cord mesenchymal stem cells in patients with diabetic foot ulcer and peripheral arterial disease: a phase I pilot study with a 3-year follow-up
Authors: Zhang Che , Huang Li , Wang Xiaofen , Zhou Xiaoya , Zhang Xiaoxian , Li Ling , Wu Jieying , Kou Meng , Cai Cheguo , Lian Qizhou , Zhou Xihui 
Published: September 2022

AbstractBackgroundDiabetic foot ulcer (DFU) is a serious chronic complication of diabetes mellitus that contributes to 85% of nontraumatic lower extremity amputations in diabetic patients. Preliminary clinical benefits have been shown in treatments based on mesenchymal stem cells for patients with DFU or peripheral arterial disease (PAD). However, the long-term safety and benefits are unclear for patients with both DFU and PAD who are not amenable to surgical revascularization.MethodsIn this phase I pilot study, 14 patients with PAD and incurable DFU were enrolled to assess the safety and efficacy of human umbilical cord mesenchymal stem cell (hUC-MSC) administration based on conservative treatments. All patients received topical and intravenous administrations of hUC-MSCs at a dosage of 2 × 105cells/kg with an upper limit of 1 × 107cells for each dose. The adverse events during treatment and follow-up were documented for safety assessments. The therapeutic efficacy was assessed by ulcer healing status, recurrence rate, and 3-year amputation-free rate in the follow-up phase.ResultsThe safety profiles were favorable. Only 2 cases of transient fever were observed within 3 days after transfusion and considered possibly related to hUC-MSC administration intravenously. Ulcer disclosure was achieved for more than 95% of the lesion area for all patients within 1.5 months after treatment. The symptoms of chronic limb ischaemia were alleviated along with a decrease in Wagner scores, Rutherford grades, and visual analogue scale scores. No direct evidence was observed to indicate the alleviation of the obstruction in the main vessels of target limbs based on computed tomography angiography. The duration of rehospitalization for DFU was 2.0 ± 0.6 years. All of the patients survived without amputation due to the recurrence of DFU within 3 years after treatments.ConclusionsBased on the current pilot study, the preliminary clinical benefits of hUC-MSCs on DFU healing were shown, including good tolerance, a shortened healing time to 1.5 months and a favorable 3-year amputation-free survival rate. The clinical evidence in the current study suggested a further phase I/II study with a larger patient population and a more rigorous design to explore the efficacy and mechanism of hUC-MSCs on DFU healing.Trial registration: The current study was registered retrospectively on 22 Jan 2022 with the Chinese Clinical Trial Registry (ChiCTR2200055885),http://www.chictr.org.cn/showproj.aspx?proj=135888Graphical Abstract
Hsa_circ_0001485 promoted osteogenic differentiation by targeting BMPR2 to activate the TGFβ-BMP pathway
Authors: Chen Shan-Chuang , Jiang Tao , Liu Qi-Yu , Liu Zi-Tao , Su Yu-Fei , Su Hai-Tao 
Published: September 2022

Abstract
Background
Circular RNAs (circRNAs) are a new type of stable noncoding RNA and have been proven to play a crucial role in osteoporosis. This study explored the role and mechanism of hsa_circ_0001485 in osteogenic differentiation.

Methods
Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene Ontology (GO) enrichment analysis were performed according to the previous sequencing data in human bone marrow mesenchymal stem cells (BMSC) before and after the induction of osteogenic differentiation on the differentially expressed circRNAs, to screen out signaling pathways associated with osteogenic differentiation. The hFOB 1.19 cells were used to verify the function and mechanism of specific circRNAs in osteogenic differentiation. Additionally, small interfering fragments and overexpression plasmids were used to determine the role of specific circRNAs during osteogenic differentiation. Furthermore, pull-down experiments and mass spectrometry were performed to determine the proteins that bind to specific circRNAs.

Results
The KEGG and GO enrichment analyses showed that the TGFβ-BMP signaling pathway was related to the osteogenic differentiation process, and four circRNAs were associated with the pathway. The quantitative polymerase chain reaction analysis revealed that hsa_circ_0001485 expression was increased during the osteogenic differentiation process of BMSCs. Knockdown of hsa_circ_0001485 suppressed the activity of the alkaline phosphatase enzyme and the expression of RUNX2, osteopontin, and osteocalcin in the osteogenic hFOB 1.19 cells, whereas overexpression of hsa_circ_0001485 promoted their expression. Additionally, we found that hsa_circ_0001485 and BMPR2 targeted binding to activate the TGFβ-BMP signaling pathway and promoted osteogenic differentiation through mass spectrometry analysis.

Conclusion
This study demonstrates that hsa_circ_0001485 is highly expressed in the osteogenic hFOB 1.19 cells, which activate the TGFβ-BMP pathway through targeted binding of BMPR2, and plays a positive role in regulating osteogenic differentiation.
Exopolysaccharide of Enterococcus faecium L15 promotes the osteogenic differentiation of human dental pulp stem cells via p38 MAPK pathway
Authors: Kim Hyewon , Oh Naeun , Kwon Mijin , Kwon Oh-Hee , Ku Seockmo , Seo Jeongmin , Roh Sangho 
Published: September 2022

AbstractBackgroundBone has important functions in the body. Several researchers have reported that the polysaccharides and lipopolysaccharide derived from microbes can promote osteogenic differentiation of stem cells.Enterococcus faecium,a lactic acid bacterium (LAB), produces several bioactive metabolites and has been widely applied in the food and nutraceutical industries. The exopolysaccharide (EPS) from LAB has also been extensively examined for its postbiotic effects and for its in vivo and in vitro functionalities. However, studies on promoting bone differentiation using polysaccharides from LAB are lacking. Therefore, the purpose of this study was to investigate the effect ofE. faeciumL15 extract and EPS on osteogenic differentiation of human dental pulp stem cells (hDPSCs) and to identify the underlying mechanisms.MethodshDPSCs were obtained from dental pulp tissue, and L15 extract and EPS were isolated from L15. Gene and protein expression of the osteogenic differentiation markers were analyzed with qPCR and western blotting and the possible signaling pathways were also investigated using western blotting. Osteogenic differentiation potential was examined by alkaline phosphatase (ALP) staining and alizarin red s (ARS) staining. In addition, osteogenic differentiation potential of L15 EPS was explored in ex vivo culture of neonate murine calvaria.ResultsThe calcium deposition and ALP activity were enhanced by addition of L15 extract or EPS. The expression levels ofRUNX2,ALP, andCOL1A1mRNA and the protein expression levels of RUNX2, ALP, and BMP4 were increased in hDPSCs treated with the L15 extract or EPS. The L15 EPS treatment enhanced phosphorylation of the p38 mitogen-activated protein kinase (MAPK). The L15 EPS-induced increases in RUNX2, ALP, and BMP4 expression were suppressed by the p38 MAPK inhibitor SB203580. The promoting effect of L15 EPS on osteogenic differentiation was not only seen in hDPSCs, but also in osteoblast precursors. ALP activity and the expression ofRUNX2,ALP, andCOL1A1increased in the L15 EPS-treated osteoblast precursors. In addition, L15 EPS increased bone thickness of neonate murine calvaria in ex vivo culture.ConclusionsThe stimulatory effect of L15 extract and EPS on osteogenic differentiation occurred through the p38 MAPK pathway, and L15 EPS enhanced new bone formation in neonate murine calvaria. These data suggest that L15 EPS has therapeutic potential applicable to bone regeneration.
Efficacy of stem cell therapy in animal models of intracerebral hemorrhage: an updated meta-analysis
Authors: Li Chenchen , Qin Haiyun , Zeng Liuwang , Hu Zhiping , Chen Chunli 
Published: September 2022

Abstract
Background
Multiple studies have reported that stem cell therapy has beneficial effects in animal models of intracerebral hemorrhage (ICH). However, this finding remains inconclusive. This study was performed to systematically determine the effect size of stem cell therapy in ICH animal models by pooling and analyzing data from newly published studies.

Methods
A literature search identified studies of stem cells in animal models of ICH. We searched mainstream databases from inception to November, 2021. And pooled effect size of stem cells was determined for diversified neurobehavioral scales and structural endpoints using random effects models.

Results
The median quality score of 62 included studies was 5.32. Our results revealed an overall positive effect of stem cell therapy. More specifically, the SMD was − 2.27 for mNSS, − 2.14 for rotarod test, − 2.06 for MLPT, − 1.33 for cylinder test, − 1.95 for corner turn test, − 1.42 for tissue loss, and − 1.86 for brain water content. For mNSS, classifying comparisons by quality score showed significant differences in estimates of effect size (p = 0.013), and high-quality comparisons showed a better outcome (SMD = − 2.57) compared with low-quality comparisons (SMD = − 1.59). Besides, different delivery routes also showed a significant difference in the estimates of effect size for mNSS (p = 0.002), and the intraperitoneal route showed the best outcome (SMD = − 4.63). For tissue loss, the autologous blood-induced ICH model showed a better outcome (SMD = − 1.84) compared with the collagenase-induced ICH model (SMD = − 0.94, p = 0.035). Additionally, stem cell therapy initiated within 8 h post-ICH showed the greatest efficacy on tissue loss reduction, followed by initiated with 24 h post-ICH. Finally, stem cells with different sources and types showed similar beneficial effects for mNSS as well as tissue loss.

Conclusions
Our results suggested that stem cell therapy had remarkable benefits on ICH animals on both the functional and structural outcomes in animal models of ICH, with very large effect size. These findings support the utility of further studies to translate stem cells in the treatment of ICH in humans. Moreover, the results should be interpreted in the light of the limitations in experimental design and the methodological quality of the studies included in the meta-analysis.
Optimal imaging time points considering accuracy and precision of Patlak linearization for 89Zr-immuno-PET: a simulation study
Authors: Wijngaarden Jessica E. , Huisman Marc C. , Pouw Johanna E. E. , Menke-van der Houven van Oordt C. Willemien , Jauw Yvonne W. S. , Boellaard Ronald 
Published: September 2022

Abstract
Purpose
Zirconium-89-immuno-positron emission tomography (89Zr-immuno-PET) has enabled visualization of zirconium-89 labelled monoclonal antibody (89Zr-mAb) uptake in organs and tumors in vivo. Patlak linearization of 89Zr-immuno-PET quantification data allows for separation of reversible and irreversible uptake, by combining multiple blood samples and PET images at different days. As one can obtain only a limited number of blood samples and scans per patient, choosing the optimal time points is important. Tissue activity concentration curves were simulated to evaluate the effect of imaging time points on Patlak results, considering different time points, input functions, noise levels and levels of reversible and irreversible uptake.

Methods
Based on 89Zr-mAb input functions and reference values for reversible (VT) and irreversible (Ki) uptake from literature, multiple tissue activity curves were simulated. Three different 89Zr-mAb input functions, five time points between 24 and 192 h p.i., noise levels of 5, 10 and 15%, and three reference Ki and VT values were considered. Simulated Ki and VT were calculated (Patlak linearization) for a thousand repetitions. Accuracy and precision of Patlak linearization were evaluated by comparing simulated Ki and VT with reference values.

Results
Simulations showed that Ki is always underestimated. Inclusion of time point 24 h p.i. reduced bias and variability in VT, and slightly reduced bias and variability in Ki, as compared to combinations of three later time points. After inclusion of 24 h p.i., minimal differences were found in bias and variability between different combinations of later imaging time points, despite different input functions, noise levels and reference values.

Conclusion
Inclusion of a blood sample and PET scan at 24 h p.i. improves accuracy and precision of Patlak results for 89Zr-immuno-PET; the exact timing of the two later time points is not critical.
Change in brain amyloid load and cognition in patients with amnestic mild cognitive impairment: a 3-year follow-up study
Authors: Rauhala Elina , Johansson Jarkko , Karrasch Mira , Eskola Olli , Tolvanen Tuula , Parkkola Riitta , Virtanen Kirsi A. , Rinne Juha O. 
Published: September 2022

Abstract
Background
Our aim was to investigate the discriminative value of 18F-Flutemetamol PET in longitudinal assessment of amyloid beta accumulation in amnestic mild cognitive impairment (aMCI) patients, in relation to longitudinal cognitive changes.

Methods
We investigated the change in 18F-Flutemetamol uptake and cognitive impairment in aMCI patients over time up to 3 years which enabled us to investigate possible association between changes in brain amyloid load and cognition over time. Thirty-four patients with aMCI (mean age 73.4 years, SD 6.6) were examined with 18F-Flutemetamol PET scan, brain MRI and cognitive tests at baseline and after 3-year follow-up or earlier if the patient had converted to Alzheimer´s disease (AD). 18F-Flutemetamol data were analyzed both with automated region-of-interest analysis and voxel-based statistical parametric mapping.

Results
18F-flutemetamol uptake increased during the follow-up, and the increase was significantly higher in patients who were amyloid positive at baseline as compared to the amyloid-negative ones. At follow-up, there was a significant association between 18F-Flutemetamol uptake and MMSE, logical memory I (immediate recall), logical memory II (delayed recall) and verbal fluency. An association was seen between the increase in 18F-Flutemetamol uptake and decline in MMSE and logical memory I scores.

Conclusions
In the early phase of aMCI, presence of amyloid pathology at baseline strongly predicted amyloid accumulation during follow-up, which was further paralleled by cognitive declines. Inversely, some of our patients remained amyloid negative also at the end of the study without significant change in 18F-Flutemetamol uptake or cognition. Future studies with longer follow-up are needed to distinguish whether the underlying pathophysiology of aMCI in such patients is other than AD.
Population history, genetic variation, and conservation status of European white elm (Ulmus laevis Pall.) in Poland
Authors: Litkowiec Monika , Chudzińska Magdalena , Pasławska Anna , Pałucka Małgorzata , Kozioł Czesław , Lewandowski Andrzej 
Published: September 2022

Abstract
Key message
The core populations of the European white elm (Ulmus laevis Pall.) located in Poland maintained slightly higher level of genetic diversity compared to the peripheral populations of this species.

Context
The most severe threat to elms is the loss of natural habitat under the pressures of agriculture and forestry as well as urbanization. The reductions in European white elm populations as well as populations of other elm species have also been caused by Dutch elm disease (DED). Previous studies have indicated a low level of genetic variation in Ulmus leavis Pall. However, in Poland, the genetic resources and demographic history of U. laevis populations remain poorly documented.

Aims
The genetic resources of U. laevis in Poland were identified and characterized. Additionally, tests were performed to identify potential bottleneck signatures and effective population sizes of the examined populations.

Methods
Polymorphism was analyzed using a set of six nuclear microsatellite markers (nSSRs) for 1672 individuals from 41 populations throughout the species range in Poland.

Results
(1) A moderate level of genetic variation was found. (2) A low genetic differentiation and lack of population structuring were identified. (3) Evidence of reduction in population size was found as a consequence of severe, past bottlenecks.

Conclusion
The loss of genetic diversity of U. laevis probably occurred in their refugia or shortly after the postglacial recolonization. This loss may have been affected by past DED pandemics similar to those seen at present.
Asynchronous dissipative control for networked time-delay Markov jump systems with event-triggered scheme and packet dropouts
Authors: Chen Huiying , Liu Renwei , He Ping , Li Zuxin 
Published: September 2022

AbstractThis paper is concerned with asynchronous dissipative control for a class of networked time-delay Markov jump systems with event-triggered scheme and packet dropouts. To reduce communication consumption, an event-triggered transmission scheme is introduced. The phenomenon of packet dropout during the communication between the controller and the actuator is described by the Bernoulli model. The designed dissipative controller is asynchronous with the physical plant, which is described by a hidden Markov model. Based on a mode-dependent Lyapunov–Krasovskii function, a sufficient condition for the closed-loop control system to be stochastically stable and strictly $$(\mu ,\vartheta ,\upsilon ){-}\gamma$$

(
μ
,
ϑ
,
υ
)
-
γ

-dissipative is obtained. Furthermore, the design of dissipative controller is simplified by using matrix scaling and slack matrix techniques. Finally, a robotic arm system is used as an example to verify the effectiveness of our proposed design method.
Intelligent hyperspectral target detection for reliable IoV applications
Authors: Wang Zixu , Jin Lizuo , Yi Kaixiang 
Published: September 2022

AbstractIn recent years, hyperspectral imagery has played a significant role in IoV (Internet of Vehicles) vision areas such as target acquisition. Researchers are focusing on integrating detection sensors, detection computing units, and communication units into vehicles to expand the scope of target detection technology with hyperspectral imagery. As imaging spectroscopy technology gradually matures, the spectral resolution of captured hyperspectral images is increasing. At the same time, the volume of data is also increasing. As a result, the reliability of IoV applications is challenged. In this paper, an intelligent hyperspectral target detection method based on deep learning network is proposed. It is based on the residual network structure with the addition of an attention mechanism. The trained network model requires few computational resources and can provide the results in a short time. Our method improves the value of mAP50 by an average of 3.57% for all categories and by up to 5% for a single category on the public dataset.
A security method of hardware Trojan detection using path tracking algorithm
Authors: Huang Der-Chen , Hsiao Chun-Fang , Chang Tin-Wei , Chu Ying-Yi 
Published: September 2022

AbstractRecently, the issue of malicious circuit alteration and attack draws more attention than ever before due to the globalization of IC design and manufacturing. Malicious circuits, also known as hardware Trojans, are found able to degrade the circuit performance or even leak confidential information, and accordingly it is definitely an issue of immediate concern to develop detection techniques against hardware Trojans. This paper presents a ring oscillator-based detection technique to improve the hardware Trojan detection performance. A circuit under test is divided into a great number of blocks, path assignment is optimized using a path tracking algorithm, and a high coverage is reached accordingly.
Systematic reviews are rarely used to contextualise new results—a systematic review and meta-analysis of meta-research studies
Authors: Draborg Eva , Andreasen Jane , Nørgaard Birgitte , Juhl Carsten Bogh , Yost Jennifer , Brunnhuber Klara , Robinson Karen A. , Lund Hans 
Published: September 2022

Abstract
Background
Results of new studies should be interpreted in the context of what is already known to compare results and build the state of the science. This systematic review and meta-analysis aimed to identify and synthesise results from meta-research studies examining if original studies within health use systematic reviews to place their results in the context of earlier, similar studies.

Methods
We searched MEDLINE (OVID), EMBASE (OVID), and the Cochrane Methodology Register for meta-research studies reporting the use of systematic reviews to place results of original clinical studies in the context of existing studies. The primary outcome was the percentage of original studies included in the meta-research studies using systematic reviews or meta-analyses placing new results in the context of existing studies. Two reviewers independently performed screening and data extraction. Data were synthesised using narrative synthesis and a random-effects meta-analysis was performed to estimate the mean proportion of original studies placing their results in the context of earlier studies. The protocol was registered in Open Science Framework.

Results
We included 15 meta-research studies, representing 1724 original studies. The mean percentage of original studies within these meta-research studies placing their results in the context of existing studies was 30.7% (95% CI [23.8%, 37.6%], I2=87.4%). Only one of the meta-research studies integrated results in a meta-analysis, while four integrated their results within a systematic review; the remaining cited or referred to a systematic review. The results of this systematic review are characterised by a high degree of heterogeneity and should be interpreted cautiously.

Conclusion
Our systematic review demonstrates a low rate of and great variability in using systematic reviews to place new results in the context of existing studies. On average, one third of the original studies contextualised their results. Improvement is still needed in researchers’ use of prior research systematically and transparently—also known as the use of an evidence-based research approach, to contribute to the accumulation of new evidence on which future studies should be based.

Systematic review registration
Open Science registration number https://osf.io/8gkzu/