bluuebunny/crossref_metadata_2025 huggingface dataset:
The top 100 most cited articles on total hip arthroplasty: a bibliometric analysis
Authors: Zhang Wenchao , Tang Ning , Li Xiaopeng , George Daniel M. , He Guangxu , Huang Tianlong
Published: December 2019

Background

Over the past few decades, more and more articles about total hip arthroplasty have been published. We noticed, however, little is known about the characteristics and qualities of these studies.

Methods

The databases of Web of Science Core Collection, BIOSIS Citation Index, MEDLINE, etc. were utilized for the identification of articles published from 1990 to May 2019. Total hip arthroplasty–related articles were identified, and the 100 most cited articles were selected for subsequent analysis of citation count, citation density (citations/article age), authorship, theme, geographic distribution, time-related flux, level of evidence, and network analysis.

Results

The selected 100 articles were published mainly in the 1990s (46%) and 2000s (47%) with almost equal amount. Citations per article ranged from 994 to 191. Leading countries were the USA followed by Canada, England, and Sweden, all located in North America and Western Europe. The most highlighted study themes were postoperative thrombosis and surgical methods and materials. The most common level of evidence was level III (35%). The network analysis connoted that radiography, acetabulum, reoperation, and bone cement had a high degree of centrality in the 1990s, while cement had a high degree of centrality in the 2000s and 2010s.

Conclusions

The time, area, and theme distribution of the top 100 most cited articles in the total hip arthroplasty have been thoroughly analyzed. It is noticeable that postoperative thromboembolism currently plays a major role in the field of total hip arthroplasty researches. However, most of them focus on the effectiveness of different treatments and drugs; little is known about its underlying mechanisms and influencing factors.
Emotional and behavioral problems, quality of life and metabolic control in NTBC-treated Tyrosinemia type 1 patients
Authors: van Vliet Kimber , van Ginkel Willem G. , Jahja Rianne , Daly Anne , MacDonald Anita , De Laet Corinne , Vara Roshni , Rahman Yusof , Cassiman David , Eyskens Francois , Timmer Corrie , Mumford Nicky , Bierau Jörgen , van Hasselt Peter M. , Gissen Paul , Goyens Philippe J. , McKiernan Patrick J. , Wilcox Gisela , Morris Andrew A. M. , Jameson Elisabeth A. , Huijbregts Stephan C. J. , van Spronsen Francjan J.
Published: December 2019

Background

Treatment with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) and dietary phenylalanine and tyrosine restriction improves physical health and life expectancy in Tyrosinemia type 1 (TT1). However, neurocognitive outcome is suboptimal. This study aimed to investigate behavior problems and health-related quality of life (HR-QoL) in NTBC-dietary-treated TT1 and to relate this to phenylalanine and tyrosine concentrations.

Results

Thirty-one TT1 patients (19 males; mean age 13.9 ± 5.3 years) were included in this study. Emotional and behavioral problems, as measured by the Achenbach System of Empirically Based Assessment, were present in almost all domains. Attention and thought problems were particularly evident. HR-QoL was assessed by the TNO AZL Children’s and Adults QoL questionnaires. Poorer HR-QoL as compared to reference populations was observed for the domains: independent daily functioning, cognitive functioning and school performance, social contacts, motor functioning, and vitality. Both internalizing and externalizing behavior problems were associated with low phenylalanine (and associated lower tyrosine) concentrations during the first year of life. In contrast, high tyrosine (and associated higher phenylalanine) concentrations during life and specifically the last year before testing were associated with more internalizing behavior and/or HR-QoL problems.

Conclusions

TT1 patients showed several behavior problems and a lower HR-QoL. Associations with metabolic control differed for different age periods. This suggests the need for continuous fine-tuning and monitoring of dietary treatment to keep phenylalanine and tyrosine concentrations within target ranges in NTBC-treated TT1 patients.
Super-antibiofilm effect of N2 plasma treated buffer (NPB) against plant pathogenic bacterium
Authors: Seo Hyemi , Hong Jisoo , Kim Taeyeol , Choi Won ll , Sung Daekyung , Moon Eunpyo
Published: December 2019

Controlling of biofilms formation in numerous pathogenic bacteria is one of the most difficult tasks in the control of bacterial diseases. Plasma has attracted extensive attention due to their potential applications for effective inhibiting of biofilm. Recently, plasma-activated water (PAW) has developed as an alternative method for bacterial inactivation and disinfection of foods owing to advantages of more convenient and efficient storage and transportation than direct plasma application. However, most previous studies about PAW have only focused on the improvement of its antibacterial effect instead of antibiofilm activity. Therefore, we report the development of N2 plasma treated buffer (NPB) and the super-antibiofilm effect of NPB against Pseudomonas syringae pv. tomato DC3000 (Pst DC3000) as a plant pathogenic bacterium. Scavenger assays using various antioxidants revealed that reactive oxygen species were involved in the inhibitory cellular actions of NPB, with H2O2 and singlet oxygen proving essential for bacterial death. Intensive analysis of NPB, stored at different periods and temperatures, showed that the antimicrobial efficacy was well maintained for 3 months at − 80 °C. Importantly, further studies showed that NPB effectively inhibited not only the growth of planktonic Pst DC3000 but also biofilm formation. The remarkable inhibition on the biofilm was analyzed and visualized using LIVE/DEAD viability assays and confocal laser scanning microscopy (CLSM) imaging. The 3D CLSM imaging data revealed that the bactericidal activity of NPB was permeable enough to affect the cells embedded inside the biofilm. This prominent permeability could be a crucial feature of NPB contributing to effective super-antibiofilm.
Fire acupuncture for mild to moderate knee osteoarthritis: a protocol for a randomized controlled pilot trial
Authors: Fu Yuan-Bo , Li Bin , Sun San-Feng , Liu Hui-Lin , Wang Xin , Wang Shao-Song , Zhang Fan , Du Xin , Ge Du-Juan , Shang Lei , Liang Rui-Li , Wang Li-Na , Yuan Fang , Sun Jing-Qing , Chen Jun-Wei
Published: December 2019

Background

Knee osteoarthritis (KOA) is one of the most common bone and joint diseases. As one of the main non-drug therapies, acupuncture is widely used to treat KOA, although the evidence for its efficacy is inconclusive. The objective of this pilot trial is to clarify the clinical efficacy and safety of fire acupuncture in the treatment of mild to moderate KOA and to provide high-quality data for further research.

Methods/design

This study is a prospective randomized controlled pilot trial in which 120 patients with mild to moderate KOA will be randomly allocated in equal proportions to a fire acupuncture group or a general acupuncture group. They will receive acupuncture for six sessions over 2 weeks. The primary end point is success rate, which will be calculated based on the change from baseline of the pain and function scores in the Western Ontario and McMaster Universities Osteoarthritis Index at 4 weeks. Secondary end points include the proportion of patients achieving clinical improvement based on: (1) the OMERACT-OARSI responder criteria, (2) levels of matrix metalloproteinase 3, interleukin 1β, and tumor necrosis factor α in blood, and (3) a subjective efficacy evaluation from patients.

Trial registration

Chinese Clinical Trial Registry, ChiCTR1800019162. Registered on 29 October 2018.
Protocol for a phase III wait-listed cluster randomised controlled trial of an intervention for mental well-being through enhancing mental health literacy and improving work friendliness in Hong Kong
Authors: Lam Lawrence T. , Wong Prudence , Lam Mary K.
Published: December 2019

Background

Mental health has long been recognised as a major global health issue. Some work-related characteristics have been identified to be associated with common mental health problems, and thus the workplace is an important venue for the prevention of mental health problems and promoting mental wellness. Burnout is one of the important aspects of workplace organisational stressors and, in recent years, the lack of mental health literacy has also been identified as a fundamental issue. Studies have demonstrated that an improvement in mental health literacy is an effective measure for enhancing mental well-being. It would be prudent to combine an organisation-directed component and the enhancement of mental health literacy in an intervention programme. This trial will examine the novel approach of an intervention aiming to provide an evidence-based prevention programme.

Methods

This study utilised a wait-listed cluster randomised control trial design. Using branch offices as the primary sampling units, employees from three large companies in different industries will be recruited. Upon enrolment and after the baseline assessment of the outcome measures, participants nested in the branch offices will be allocated to the intervention or wait-listed arms. The intervention programme comprises of two main elements: an organisation-directed component and individual-directed psychoeducation training. This intervention will be delivered by a senior social worker well-versed in workplace issues over a period of 3 months. The trial will determine whether an integrated workplace mental health literacy and well-being programme is effective in increasing the mental health literacy scores and reducing burnout and stress scores, as measured by standardised and validated scales.

Discussion

If the trial results are in line with the hypothesis that supports the efficacy of the intervention programme, this will provide an evidence-based approach for an effective workplace mental well-being intervention programme that could not only enhance the understanding of mental health issues, but also reduce work-related burnout and stress as well as increase workers’ quality of life.

Trial registration

Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12619000464167. Registered prospectively on 20 March 2019.
Randomised controlled trial on vitreoretinal surgery with and without oral anticoagulants: surgical complications, visual results and perioperative thromboembolic events
Authors: Andonegui Jose , Capdevila Ferran , Zubicoa Alicia , Ibáñez Berta
Published: December 2019

Background

Vitreoretinal surgery in anticoagulated patients is a challenging situation for vitreoretinal surgeons, who have to choose between being faced with the systemic thromboembolic risks that the interruption of anticoagulation involves, or the intra- and postoperative haemorrhagic risks associated with maintenance of this therapy. So far, no trial has compared, in a prospective and randomized manner, perioperative complications and the visual results associated with continuation or interruption of oral anticoagulant therapy before pars plana vitrectomy (PPV) under retrobulbar anaesthesia. The main objective of this trial is to compare haemostasis-related perioperative complications of PPV in patients maintaining anticoagulant therapy before surgery compared to patients with an interruption in this therapy before surgery.

Methods

Ninety-six patients will be randomly assigned to either the control group, in whom oral anticoagulant therapy will be interrupted and substituted with subcutaneous heparin according to local clinical practice, or the intervention group in whom oral anticoagulant therapy will not be interrupted before surgery. Patients will be stratified according to the oral anticoagulant they were taking (direct or indirect anticoagulation). They will be followed up for 12 weeks, and the primary outcome, and haemorrhagic complications until 15 days after surgery, will be evaluated.

Discussion

This trial will provide novel information on the possibility of continuing anticoagulant therapy during PPV. The benefits expected from the change in the current surgical management paradigm for anticoagulated patients would be a decreased risk in the incidence of perioperative thromboembolic events and the possibility of performing surgery without delay and without the need for patients to change their usual anticoagulation protocol to the more complex and less safe substitutive therapy.

Trial registration

Clinical Trials Register EudraCT,2018–000753-45. Registered on 11 November 2018.
A double-masked placebo-controlled trial of azithromycin to prevent child mortality in Burkina Faso, West Africa: Community Health with Azithromycin Trial (CHAT) study protocol
Authors:   for the Étude CHAT Study Group, Sié Ali , Ouattara Mamadou , Bountogo Mamadou , Bagagnan Cheik , Coulibaly Boubacar , Boudo Valentin , Lebas Elodie , Brogdon Jessica M. , Lin Ying , Bärnighausen Till , Porco Travis C. , Doan Thuy , Lietman Thomas M. , Oldenburg Catherine E.
Published: December 2019

Background

Biannual, mass azithromycin distribution has previously been shown to reduce all-cause child mortality in sub-Saharan Africa. Subgroup analysis suggested that the strongest effects were in the youngest children, leading to the hypothesis that targeting younger age groups might be an effective strategy to prevent mortality. We present the methods of two randomized controlled trials designed to evaluate mass and targeted azithromycin distribution for the prevention of child mortality in Burkina Faso, West Africa.

Methods/design

The Child Health with Azithromycin Treatment (CHAT) study consists of two nested, randomized controlled trials. In the first, communities are randomized in a 1:1 fashion to biannual, mass azithromycin distribution or placebo. The primary outcome is under-5 all-cause mortality measured at the community level. In the second, children attending primary healthcare facilities during the first 5–12 weeks of life for a healthy child visit (e.g., for vaccination) are randomized in a 1:1 fashion to a single orally administered dose of azithromycin or placebo. The primary outcome is all-cause mortality measured at 6 months of age. The trial commenced enrollment in August 2019.

Discussion

This study is expected to provide evidence on two health systems delivery approaches (mass and targeted treatment) for azithromycin to prevent all-cause child mortality. The results will inform global and national policies related to azithromycin for the prevention of child mortality.

Trial registration

ClinicalTrials.gov, ID: NCT03676764. Registered on 19 September 2018; prospectively registered pre results.
Cryptic intermediate snail host of the liver fluke Fasciola hepatica in Africa
Authors: Mahulu Anna , Clewing Catharina , Stelbrink Björn , Chibwana Fred D. , Tumwebaze Immaculate , Russell Stothard J. , Albrecht Christian
Published: December 2019

Background

Snails such asGalba truncatulaare hosts for trematode flukes causing fascioliasis, a zoonosis that is a major public health problem.Galba truncatulahas recently been shown to be a cryptic species complex. African populations ofGalbaspp. are not yet studied using molecular assessments and is imperative to do so and reconstruct the centre of origin ofGalbaand to understand when and by what means it may have colonized the highlands of Africa and to what extent humans might have been involved in that process.

Methods

Samples from all known sub-ranges throughout Africa and new samples from Europe and Asia were obtained. We used a combination of two mitochondrial (cox1 and16S) and one nuclear (ITS2) markers and phylogenetic, divergence time estimates and phylogeographical methods to determine the identity and biogeographical affinities. We also reconstructed the colonization history including the likely mode of dispersal and tested for the presence of crypticGalbaspecies in Africa.

Results

Galba truncatulais restricted to the Palaearctic region of the continent, namely Morocco. All sub-Saharan populations proved to be a distinct species according to the phylogenetic analyses and genetic distance. We propose to use the existing nameGalba mweruensis(Connolly, 1929) for this species which is morphologically indistinguishable from the other two species hitherto known to occur in northern Africa, i.e.G. truncatulaandG. schirazensis. Sub-tropical Africa has been colonized only once in either the Pliocene and possibly Miocene. Diversification withinG. mweruensisis dated to the Plio-Pleistocene and thus human-mediated dispersal can be ruled out for the initial colonization of the isolated mountain ranges. There are potentially even more cryptic species in high altitude areas of Africa as outlined by the distinctness of the population found at the top of Mt. Elgon, Uganda.

Conclusions

From a novel genetic inspection of available African material, a hitherto neglected distinct species,G. mweruensis, now appears a major host ofF. hepaticathroughout sub-Saharan Africa. A closer examination of trematode parasites hosted by this species is needed in order to understand transmission patterns in highlands throughout eastern and southern Africa. We encourage future studies to inspect other high altitudes areas in Africa in light of parasites of either veterinary or medical importance.
Prioritization of genes driving congenital phenotypes of patients with de novo genomic structural variants
Authors: Middelkamp Sjors , Vlaar Judith M. , Giltay Jacques , Korzelius Jerome , Besselink Nicolle , Boymans Sander , Janssen Roel , de la Fonteijne Lisanne , van Binsbergen Ellen , van Roosmalen Markus J. , Hochstenbach Ron , Giachino Daniela , Talkowski Michael E. , Kloosterman Wigard P. , Cuppen Edwin
Published: December 2019

Background

Genomic structural variants (SVs) can affect many genes and regulatory elements. Therefore, the molecular mechanisms driving the phenotypes of patients carrying de novo SVs are frequently unknown.

Methods

We applied a combination of systematic experimental and bioinformatic methods to improve the molecular diagnosis of 39 patients with multiple congenital abnormalities and/or intellectual disability harboring apparent de novo SVs, most with an inconclusive diagnosis after regular genetic testing.

Results

In 7 of these cases (18%), whole-genome sequencing analysis revealed disease-relevant complexities of the SVs missed in routine microarray-based analyses. We developed a computational tool to predict the effects on genes directly affected by SVs and on genes indirectly affected likely due to the changes in chromatin organization and impact on regulatory mechanisms. By combining these functional predictions with extensive phenotype information, candidate driver genes were identified in 16/39 (41%) patients. In 8 cases, evidence was found for the involvement of multiple candidate drivers contributing to different parts of the phenotypes. Subsequently, we applied this computational method to two cohorts containing a total of 379 patients with previously detected and classified de novo SVs and identified candidate driver genes in 189 cases (50%), including 40 cases whose SVs were previously not classified as pathogenic. Pathogenic position effects were predicted in 28% of all studied cases with balanced SVs and in 11% of the cases with copy number variants.

Conclusions

These results demonstrate an integrated computational and experimental approach to predict driver genes based on analyses of WGS data with phenotype association and chromatin organization datasets. These analyses nominate new pathogenic loci and have strong potential to improve the molecular diagnosis of patients with de novo SVs.
Diagnostic performance of serum cystatin C and complement component 1q in lupus nephritis
Authors: Xu Bei , Zhang Ya-mei , Yang Yu-wei , Liu Yun-shuang , Feng Jia-fu
Published: December 2019

Background

The information concerning non-invasive, easily obtainable, and accurate biomarkers for diagnosis of lupus nephritis (LN) is extremely limited. The aim of this study was to evaluate the diagnostic performance of cystatin C (CysC) and complement component 1q (C1q) for LN.

Methods

A case-control study that included 905 patients with systemic lupus erythematosus (SLE) without LN (group SLE), 334 patients with active lupus nephritis (group LNA), 255 patients with inactive lupus nephritis (group LNI), and 497 healthy individuals (group HC) was performed in Mianyang Central Hospital from March 2017 to December 2018. The serum levels of CysC, C1q, urea (Urea), and creatinine (Creat) were measured, and 2 estimated glomerular filtration rates (eGFRCysC and eGFRCreat) were calculated by equations which were based on serum CysC established by our group and the modification of diet in renal disease (MDRD), respectively. ANOVA analysis or Kruskal-Wallis test was used for comparing the differences among the groups, and receiver operating characteristic (ROC) curve was applied to identify the diagnostic efficiencies of individual or combined multiple indicators.

Results

Significantly elevated CysC and decreased C1q were observed in the LNA and LNI groups, which was in contrast to their levels in the SLE and HC groups. CysC (AUC = 0.906) or eGFRCysC (AUC = 0.907) assessed the highest diagnostic performance on LNA when detected individually, followed by C1q (AUC = 0.753). Joint utilization of C1q and CysC achieved very good performance (AUC = 0.933) which approximated to the best one observed in the combinations of C1q, Urea, CysC, eGFRCreat, and Creat (AUC = 0.975).

Conclusion

The separately detected CysC (eGFRCysC) and C1q were superior to the conventional biomarkers Urea, Creat, and eGFRCreat in the diagnosis of LNA. Moreover, although the combined detection of Urea, Creat, C1q, CysC, and eGFRCreat had the greatest diagnostic performance, the joint utilization of CysC and C1q could be prioritized for rapid discrimination of LNA if the economic burden is taken into consideration.
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

Background

Cartilage 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).

Methods

Human 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.

Results

Cells 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.

Conclusion

Our 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

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

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

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

5G 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

Malaria 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

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. 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

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

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

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.
Immune biomarkers in thymic epithelial tumors: expression patterns, prognostic value and comparison of diagnostic tests for PD-L1
Authors: Rouquette Isabelle , Taranchon-Clermont Estelle , Gilhodes Julia , Bluthgen Maria-Virginia , Perallon Romain , Chalabreysse Lara , De Muret Anne , Hofman Veronique , Marx Alexander , Parrens Marie , Secq Veronique , Thomas de Montpreville Vincent , Galateau-Salle Françoise , Brousset Pierre , Milia Julie , Girard Nicolas , Besse Benjamin , Molina Thierry Jo , Mazières Julien
Published: December 2019

Background

Immunotherapy is currently under investigation in B3 Thymoma (TB3) and Thymic Carcinoma (TC). PD-L1 expression has been evaluated on a limited number of patients with selected antibodies. We aimed to analyze cohort of TB3 and TC with a panel of antibodies to assess the prevalence of PD-L1 expression, its prognostic value and to set up a reproducible test.

Methods

We retrospectively studied 103 patients samples of FFPE histologically confirmed TB3 (n = 53) and TC (n = 50) by expert pathologists within the RYTHMIC national network. We compared PD-L1, PD1, CD8 and PD-L2 expression and performed correlation with tumor types and patients outcomes. Four PD-L1 antibodies were tested, three of them validated as companion tests in lung cancer, one tested on two automates on whole section of tumors. We evaluated the percentage and intensity of both epithelial and immune stained cells.

Results

TB3 epithelial cells had a higher and more diffuse expression of PD-L1 than TC regardless the antibodies tested (p < 0.0001). Three out of four antibodies targeting PD-L1 tested on the DAKO autostainer gave similar staining. Concordance between antibodies was lower for PD-L1 staining on immune cells with no significant difference between TB3 and TC except on E1L3N antibody. PD-L2 antibody stained no tumor epithelial cells. High PD-L1 expression was correlated with a better overall survival for TB3 and was not correlated with tumor staging.

Conclusion

Frequent PD-L1 expression, particularly in TB3, paves the way for immunotherapy in TET (Thymic Epithelial Tumor). Otherwise, we have set up three reproducible LDT (laboratory-developed test) for four PD-L1 antibodies.
Analysing gamification elements in educational environments using an existing Gamification taxonomy
Authors: Toda Armando M. , Klock Ana C. T. , Oliveira Wilk , Palomino Paula T. , Rodrigues Luiz , Shi Lei , Bittencourt Ig , Gasparini Isabela , Isotani Seiji , Cristea Alexandra I.
Published: December 2019

Gamification has been widely employed in the educational domain over the past eight years when the term became a trend. However, the literature states that gamification still lacks formal definitions to support the design and analysis of gamified strategies. This paper analysed the game elements employed in gamified learning environments through a previously proposed and evaluated taxonomy while detailing and expanding this taxonomy. In the current paper, we describe our taxonomy in-depth as well as expand it. Our new structured results demonstrate an extension of the proposed taxonomy which results from this process, is divided into five dimensions, related to the learner and the learning environment. Our main contribution is the detailed taxonomy that can be used to design and evaluate gamification design in learning environments.