bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitro study of cartilage tissue engineering using human adipose-derived stem cells induced by platelet-rich plasma and cultured on silk fibroin scaffold
Authors: Rosadi Imam , Karina Karina , Rosliana Iis , Sobariah Siti , Afini Irsyah , Widyastuti Tias , Barlian Anggraini 
Published: December 2019

AbstractBackgroundCartilage tissue engineering is a promising technique for repairing cartilage defect. Due to the limitation of cell number and proliferation, mesenchymal stem cells (MSCs) have been developed as a substitute to chondrocytes as a cartilage cell-source. This study aimed to develop cartilage tissue from human adipose-derived stem cells (ADSCs) cultured on aBombyx morisilk fibroin scaffold and supplemented with 10% platelet-rich plasma (PRP).MethodsHuman ADSCs and PRP were characterized. A silk fibroin scaffold with 500 μm pore size was fabricated through salt leaching. ADSCs were then cultured on the scaffold (ADSC-SS) and supplemented with 10% PRP for 21 days to examine cell proliferation, chondrogenesis, osteogenesis, and surface marker expression. The messenger ribonucleic acid (mRNA) expression of type 2 collagen, aggrecan, and type 1 collagen was analysed. The presence of type 2 collagen confirming chondrogenesis was validated using immunocytochemistry. The negative and positive controls were ADSC-SS supplemented with 10% foetal bovine serum (FBS) and ADSC-SS supplemented with commercial chondrogenesis medium, respectively.ResultsCells isolated from adipose tissue were characterized as ADSCs. Proliferation of the ADSC-SS PRP was significantly increased (p < 0.05) compared to that of controls. Chondrogenesis was observed in ADSC-SS PRP and was confirmed through the increase in glycosaminoglycans (GAG) and transforming growth factor-β1 (TGF-β1) secretion, the absence of mineral deposition, and increased surface marker proteins on chondrogenic progenitors. The mRNA expression of type 2 collagen in ADSC-SS PRP was significantly increased (p < 0.05) compared to that in the negative control on days 7 and 21; however, aggrecan was significantly increased on day 14 compared to the controls. ADSC-SS PRP showed stable mRNA expression of type 1 collagen up to 14 days and it was significantly decreased on day 21. Confocal analysis showed the presence of type 2 collagen in the ADSC-SS PRP and positive control groups, with high distribution outside the cells forming the extracellular matrix (ECM) on day 21.ConclusionOur study showed that ADSC-SS with supplemented 10% PRP medium can effectively support chondrogenesis of ADSCs in vitro and promising for further development as an alternative for cartilage tissue engineering in vivo.
Mesenchymal stem cells induce dendritic cell immune tolerance via paracrine hepatocyte growth factor to alleviate acute lung injury
Authors: Lu Zhonghua , Chang Wei , Meng Shanshan , Xu Xiuping , Xie Jianfeng , Guo Fengmei , Yang Yi , Qiu Haibo , Liu Ling 
Published: December 2019

Abstract
Background
Mesenchymal stem cells (MSCs) have been shown to alleviate acute lung injury (ALI) via paracrine hepatocyte growth factor (HGF) and to induce the differentiation of dendritic cells (DCs) into tolerogenic dendritic cells (DCregs) and participate in the immune response. However, whether MSCs induce the production of DCregs by secreting HGF to alleviate early ALI remains unclear. We observed that the protective effect of mouse bone marrow-derived MSCs against lipopolysaccharide (LPS)-induced ALI was achieved by inducing mature DCs (mDCs) to differentiate into DCregs, and its mechanism is related to the activation of the HGF/Akt pathway.

Methods
MSCs or MSCs with overexpression or knockdown of HGF were cocultured with DCs derived from mouse bone marrow using a Transwell system for 3 days. Moreover, we used MSCs or MSCs with overexpression or knockdown of HGF to treat LPS-induced ALI mice for 24 h. Flow cytometry was performed to measure the phagocytosis, accumulation, and maturation of DCs, as well as proliferation of T cells. Lung injury was estimated by lung wet weight to body weight ratio (LWW/BW) and histopathological analysis. Furthermore, we used the Akt inhibitor MK-2206 in a coculture system to elucidate the role of the HGF/Akt pathway in regulating the differentiation of DCs into regulatory DCs and relieving lung injury in early ALI mice.

Results
Immature DCs (imDCs) were induced to mature after 24 h of LPS (50 ng/ml) stimulation. MSCs or HGF induced the differentiation of mDCs into regulatory DCs characterized by low expression of MHCII, CD86, and CD40 molecules, strong phagocytic function, and the ability to inhibit T cell proliferation. The effect of MSCs on DCregs was enhanced with the increase in HGF secretion and was weakened with the decrease in HGF secretion. DCregs induced by recombinant HGF were attenuated by the Akt inhibitor MK-2206. Lung DC aggregation and mDC ratio increased in LPS-induced ALI mice, while treatment with MSCs decreased lung DC aggregation and maturation and alleviated lung pathological injury. High expression of the HGF gene enhanced the above effect of MSCs, while decreased expression of HGF weakened the above effect of MSCs.

Conclusions
MSCs alleviate early ALI via paracrine HGF by inducing mDCs to differentiate into regulatory DCs. Furthermore, the mechanism of HGF-induced differentiation of mDCs into DCregs is related to the activation of the Akt pathway.
Immunomodulatory effects of interferon-γ on human fetal cardiac mesenchymal stromal cells
Authors: Grinnemo Karl-Henrik , Löfling Marie , Nathanson Lubov , Baumgartner Roland , Ketelhuth Daniel F. J. , Beljanski Vladimir , Davies Lindsay C. , Österholm Cecilia 
Published: December 2019

Abstract
Background
Mesenchymal stromal cells (MSCs), due to their regenerative and immunomodulatory properties, are therapeutically used for diseases, including heart failure. As early gestational-phase embryonic tissues exhibit extraordinary regenerative potential, fetal MSCs exposed to inflammation offer a unique opportunity to evaluate molecular mechanisms underlying preferential healing, and investigate their inherent abilities to communicate with the immune system during development. The principal aim of this study was to evaluate the effects of interferon-γ (IFNγ) on the immunomodulatory effects of first-trimester human fetal cardiac (hfc)-MSCs.

Methods
hfcMSCs (gestational week 8) were exposed to IFNγ, with subsequent analysis of the whole transcriptome, based on RNA sequencing. Exploration of surface-expressed immunoregulatory mediators and modulation of T cell responses were performed by flow cytometry. Presence and activity of soluble mediators were assessed by ELISA or high-performance liquid chromatography.

Results
Stimulation of hfcMSCs with IFNγ revealed significant transcriptional changes, particularly in respect to the expression of genes belonging to antigen presentation pathways, cell cycle control, and interferon signaling. Expression of immunomodulatory genes and associated functional changes, including indoleamine 2,3-dioxygenase activity, and regulation of T cell activation and proliferation via programmed cell death protein (PD)-1 and its ligands PD-L1 and PD-L2, were significantly upregulated. These immunoregulatory molecules diminished rapidly upon withdrawal of inflammatory stimulus, indicating a high degree of plasticity by hfcMSCs.

Conclusions
To our knowledge, this is the first study performing a systematic evaluation of inflammatory responses and immunoregulatory properties of first-trimester cardiac tissue. In summary, our study demonstrates the dynamic responsiveness of hfcMSCs to inflammatory stimuli. Further understanding as to the immunoregulatory properties of hfcMSCs may be of benefit in the development of novel stromal cell therapeutics for cardiovascular disease.
Xenofree generation of limbal stem cells for ocular surface advanced cell therapy
Authors: Nieto-Nicolau Nuria , Martínez-Conesa Eva M. , Velasco-García Alba M. , Aloy-Reverté Caterina , Vilarrodona Anna , Casaroli-Marano Ricardo P. 
Published: December 2019

Abstract
Background
Limbal stem cells (LSC) sustain the corneal integrity and homeostasis. LSC deficiency (LSCD) leads to loss of corneal transparency and blindness. A clinical approach to treat unilateral LSCD comprises autologous cultured limbal epithelial stem cell transplantation (CLET). CLET uses xenobiotic culture systems with potential zoonotic transmission risks, and regulatory guidelines make necessary to find xenofree alternatives.

Methods
We compared two xenofree clinical grade media and two feeder layers. We used CnT07, a defined commercial medium for keratinocytes, and a modified xenofree supplemented hormonal epithelial medium with human serum (XSHEM). Optimal formulation was used to compare two feeder layers: the gold standard 3T3 murine fibroblasts and human processed lipoaspirate cells (PLA). We tested the expressions of ΔNp63α and cytokeratin 3 and 12 by qPCR and immunofluorescence. Morphology, viability, clonogenicity, proliferation, and cell growth assays were carried out. We also evaluated interleukin 6 (IL-6) and stromal-derived factor 1 (SDF-1) by qPCR and ELISA.

Results
XSHEM maintained better LSC culture viability and morphology than CnT07. Irradiated PLA feeder cells improved the undifferentiated state of LSC and enhanced their growth and clonogenicity stimulating IL-6 secretion and SDF-1 expression, as well as increased proliferation and cell growth when compared with irradiated 3T3 feeder cells.

Conclusions
The combination of XSHEM and PLA feeder cells efficiently sustained LSC xenofree cultures for clinical application. Moreover, PLA feeder layers were able to improve the LSC potential characteristics. Our results would have direct clinical application in CLET for advanced therapy.

Graphical abstract
5G wireless P2MP backhaul security protocol: an adaptive approach
Authors: Kim Jiyoon , Choudhary Gaurav , Heo Jaejun , Duguma Daniel Gerbi , You Ilsun 
Published: December 2019

Abstract5G has introduced various emerging demands for new services and technologies that raised the bar for quality of service, latency, handovers, and data rates. Such diverse and perplexing network requirements bring numerous issues, among which security stands in the first row. The backhaul, which can be implemented as a wired or wireless solution, serves as a bridge between the radio access and core networks assuring connectivity to end users. The recent trends in backhaul usage rely on wireless technologies implemented using point-to-point (PTP) or point-to-multipoint (P2MP) configurations. Unfortunately, due to the nature of the transmission medium, the wireless backhaul is vulnerable and exposed to more various security threats and attacks than the wired one. In order to protect the backhaul, there have been several researches, whose authentication and key exchange scheme mainly depends on the existing security standards such as transport layer security (TLS), Internet Key Exchange version 1 (IKEv1), IKEv2, Host Identity Protocol (HIP), and Authentication and Key Agreement (AKA). However, such security standards cannot completely fulfil the security requirements including security policy update, key update, and balancing between security and efficiency, which are necessary for the emerging 5G networks. This is basically the motive behind why we study and propose a new security protocol for the backhaul link of wireless access network based on P2MP model. The proposed protocol is designed to be 5G-aware, and provides mutual authentication, perfect forward secrecy, confidentiality, integrity, secure key exchange, security policy update, key update, and balancing trade-off between efficiency and security while preventing resource exhaustion attacks. The protocol’s correctness is formally verified by the well-known formal security analysis tools: BAN-logic and Scyther. Moreover, the derived lemmas prove that the security requirements are satisfied. Finally, from a comparison analysis, it is shown that the proposed protocol is better than other standard protocols.
Optimal control in a malaria model: intervention of fumigation and bed nets
Authors: Handari Bevina D. , Vitra Febyan , Ahya Radhiya , Nadya S. Tengku , Aldila Dipo 
Published: December 2019

AbstractMalaria is one of the world’s most serious health problems because of the increasing number of cases every year. First, we discuss a deterministic model of epidemic SIR-SI spread of malaria with the intervention of bed nets and fumigation. We found that the malaria-free equilibrium is locally asymptotically stable (LAS) when $\mathcal{R}_{0} <1$R0<1 and unstable otherwise. A malaria endemic equilibrium exists and is LAS when $\mathcal{R}_{0} >1$R0>1. Sensitivity analysis of $\mathcal{R}_{0} $R0 shows that the use of bed nets and fumigation can reduce $\mathcal{R}_{0}$R0. We modify the previous model into a stochastic differential equation model to understand the effect of random environmental factors on the spread of malaria. Numerical simulations show that when $\mathcal{R}_{0} >1$R0>1, a greater value of noise intensity σ generates a solution that is different from a deterministic solution; when $\mathcal{R}_{0} <1$R0<1, regardless of the σ value, the solution approaches a deterministic solution. Then the deterministic model was modified into an optimal control model to determine the best strategy in controlling the spread of malaria by using fumigation as the control variable. Numerical simulations show that periodic fumigations cost less than constant intervention and can reduce the number of infected humans. Priority is given to the endemic prevention strategy rather than to the endemic reduction strategy. For more effective intervention, the value of $\mathcal{R}_{0}$R0 should receive close attention. A potentially endemic ($\mathcal{R}_{0}>1$R0>1) environment requires more frequent fumigation than an environment that is not potentially endemic ($\mathcal{R}_{0}<1$R0<1). A combination of the use of bed nets and fumigation can reduce the number of infected individuals at minimal cost.
Secure end-to-end processing of smart metering data
Authors: Brito Andrey , Fetzer Christof , Köpsell Stefan , Pietzuch Peter , Pasin Marcelo , Felber Pascal , Fonseca Keiko , Rosa Marcelo , Gomes Luiz , Riella Rodrigo , Prado Charles , Rust Luiz F. , Lucani Daniel E. , Sipos Márton , Nagy László , Fehér Marcell 
Published: December 2019

AbstractCloud computing considerably reduces the costs of deploying applications through on-demand, automated and fine-granular allocation of resources. Even in private settings, cloud computing platforms enable agile and self-service management, which means that physical resources are shared more efficiently. Cloud computing considerably reduces the costs of deploying applications through on-demand, automated and fine-granular allocation of resources. Even in private settings, cloud computing platforms enable agile and self-service management, which means that physical resources are shared more efficiently. Nevertheless, using shared infrastructures also creates more opportunities for attacks and data breaches. In this paper, we describe the SecureCloud approach. The SecureCloud project aims to enable confidentiality and integrity of data and applications running in potentially untrusted cloud environments. The project leverages technologies such as Intel SGX, OpenStack and Kubernetes to provide a cloud platform that supports secure applications. In addition, the project provides tools that help generating cloud-native, secure applications and services that can be deployed on potentially untrusted clouds. The results have been validated in a real-world smart grid scenario to enable a data workflow that is protected end-to-end: from the collection of data to the generation of high-level information such as fraud alerts.
Developing content for national population health surveys: an example using a newly developed sedentary behaviour module
Authors: Prince Stephanie A. , Butler Gregory P. , Roberts Karen C. , Lapointe Pam , MacKenzie Andrew M. , Colley Rachel C. , Foley Maria , Saunders Travis J. , Thompson Wendy 
Published: December 2019

Abstract
Background
While physical (in) activity surveillance has grown and continues to grow globally, surveillance of sedentary behaviour is in its infancy. As surveillance evolves to meet the changing nature of these behaviours, there is a need for the development of national health survey questions to provide accurate and consistent measures over time. The development of national health survey content is a complex, detailed and often undocumented process. The objective of this paper is to outline the process that the Public Health Agency of Canada (PHAC) and Statistics Canada took in partnership with academic experts to develop a short, flexible, sedentary behaviour module for the Canadian Health Measures Survey (CHMS) and to provide an approach for the development of future survey content.

Methods
Development of the module followed a multi-step process. The results of this paper describe this process and present a framework for content development.

Results
Initially, PHAC and Statistics Canada analysts worked together to identify key content required for a potential survey module. Next, this work was formalized through a contract with academic experts, the scope included a: review of existing Canadian sedentary behaviour modules; literature review linking different sedentary behaviours to health outcomes; and, international scan of modules currently in use in large national health surveys and research. The key output from both review processes was recommendations for a short sedentary behaviour questionnaire module (International Sedentary Assessment Tool). These recommendations provided an evidence-informed basis for discussions about how to revise and update the CHMS sedentary behaviour questionnaire content. Qualitative testing was undertaken and a final module was developed using survey design best practices.

Conclusions
Content volume in national surveys is limited due to demand to measure core content in addition to emerging health topics while keeping surveys as short as possible. Questions must therefore, be concise, valid/reliable, evidence-based, and developed using best practices. The paper describes the development process of a new survey module addressing the emerging area of sedentary behaviour for use in a national survey that may serve as a model for future population survey content development.
A multimodal intervention program to control a long-term Acinetobacter baumannii endemic in a tertiary care hospital
Authors:   In representation of A. baumannii eradication program, Valencia-Martín R. , Gonzalez-Galan V. , Alvarez-Marín R. , Cazalla-Foncueva A. M. , Aldabó T. , Gil-Navarro M. V. , Alonso-Araujo I. , Martin C. , Gordon R. , García-Nuñez E. J. , Perez R. , Peñalva G. , Aznar J. , Conde M. , Cisneros J. M. 
Published: December 2019

Abstract
Background
Acinetobacter baumannii causes frequently nosocomial infections worldwide. Its ability to survive on dry surfaces facilitates its spread and the persistence of endemic situations, especially in the intensive care units (ICUs).
The objective of this paper is to describe a multicomponent intervention program designed to control a hyperendemic persistence of multidrug-resistant A. baumannii (MDR-Ab) and to characterize its impact.

Methods
Design: Quasi-experimental intervention study based on open cohorts.
Setting: Public tertiary referral centre. Period: January 2009–August 2017.
Intervention: multifaceted program based on environmental decontamination, hand hygiene, antimicrobial stewardship, contact precautions, active surveillance, weekly reports and regular meetings.
Analysis: joinpoint regression and interrupted time-series analysis.

Results
The intervention was successfully implemented. Through the study period, the compliance with contact precautions changed from 0 to 100% and with hand hygiene, from 41.8 to 82.3%. Between 2012 and 2016, the antibiotic consumption decreased from 165.35 in to 150.44 daily-defined doses/1000 patients-days in the ICU. The incidence density of MDR-Ab in the ICU was 10.9 cases/1000 patients-days at the beginning of the intervention. After this moment, the evolution of the incidence density of MDR-Ab was: between months 0 and 6°, it remained stable; between months 7° and 10°: there was an intense decrease, with an average monthly percentage change (AMPC) = − 30.05%; from 11° month until the end, the decrease was lighter but continuous (AMPC:-2.77%), achieving an incidence density of 0 cases/1000 patients-days on the 18° month, without any new case for 12 months. From the 30° month until the end of the study period, several little outbreaks of MDR-Ab were detected, all of them rapidly controlled. The strains of MDR-Ab isolated during these outbreaks were not clonally related with the previously endemic one, which supports its eradication from the environmental reservoirs.

Conclusion
The multicomponent intervention performed by a multidisciplinary team was effective to eradicate the endemic MDR-Ab.
Factors affecting cell-free DNA fetal fraction: statistical analysis of 13,661 maternal plasmas for non-invasive prenatal screening
Authors: Hou Yaping , Yang Jiexia , Qi Yiming , Guo Fangfang , Peng Haishan , Wang Dongmei , Wang Yixia , Luo Xiaohui , Li Yi , Yin Aihua 
Published: December 2019

Abstract
Background
The identification of cell-free fetal DNA (cffDNA) facilitated non-invasive prenatal screening (NIPS) through analysis of cffDNA in maternal plasma. However, challenges regarding its clinical implementation become apparent. Factors affecting fetal fraction should be clarified to guide its clinical application.

Results
A total of 13,661 pregnant subjects with singleton pregnancies who undertook NIPS were included in the study. Relationship of gestational age, maternal BMI, and maternal age with the cffDNA fetal fraction in maternal plasmas for NIPS was investigated. Compared with 13 weeks (12.74%) and 14–18 weeks group (12.73%), the fetal fraction in gestational ages of 19–23 weeks, 24–28 weeks, and more than 29 weeks groups significantly increased to 13.11%, 16.14%, and 21.17%, respectively (P < 0.01). Compared with fetal fraction of 14.54% in the maternal BMI group of < 18.5 kg/m2, the percentage of fetal fraction in the group of 18.5–24.9 kg/m2 (13.37%), 25–29.9 kg/m2 (12.20%), 30–34.9 kg/m2 (11.32%), and 35–39.9 kg/m2 (11.57%) decreased significantly (P < 0.01). Compared with the fetal fraction of 14.38% in the group of 18–24 years old, the fetal fraction in the maternal age group of 25–29 years old group (13.98%) (P < 0.05), 30–34 years old group (13.18%) (P < 0.01), 35–39 years old group (12.34%) (P < 0.01), and ≥ 40 years old (11.90%) group (P < 0.01) decreased significantly.

Conclusions
The percentage of fetal fraction significantly increased with increase of gestational age. Decreased fetal fraction with increasing maternal BMI was found. Maternal age was also negatively related to the fetal fraction.