bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatitis E virus replication and interferon responses in human placental cells
Authors: Knegendorf Leonard , Drave Svenja A. , Dao Thi Viet Loan , Debing Yannick , Brown Richard J. P. , Vondran Florian W. R. , Resner Kathrin , Friesland Martina , Khera Tanvi , Engelmann Michael , Bremer Birgit , Wedemeyer Heiner , Behrendt Patrick , Neyts Johan , Pietschmann Thomas , Todt Daniel , Steinmann Eike
Published: January 2018

Hepatitis E virus (HEV) is a member of the genus Orthohepevirus in the family Hepeviridae and the causative agent of hepatitis E in humans. HEV is a major health problem in developing countries, causing mortality rates up to 25% in pregnant women. However, these cases are mainly reported for HEV genotype (gt)1, while gt3 infections are usually associated with subclinical courses of disease. The pathogenic mechanisms of adverse maternal and fetal outcome during pregnancy in HEV‐infected pregnant women remain elusive. In this study, we observed that HEV is capable of completing the full viral life cycle in placental‐derived cells (JEG‐3). Following transfection of JEG‐3 cells, HEV replication of both HEV gts could be observed. Furthermore, determination of extracellular and intracellular viral capsid levels, infectivity, and biophysical properties revealed production of HEV infectious particles with similar characteristics as in liver‐derived cells. Viral entry was analyzed by infection of target cells and detection of either viral RNA or staining for viral capsid protein by immunofluorescence. HEV gt1 and gt3 were efficiently inhibited by ribavirin in placental as well as in human hepatoma cells. In contrast, interferon‐α sensitivity was lower in the placental cells compared to liver cells for gt1 but not gt3 HEV. Simultaneous determination of interferon‐stimulated gene expression levels demonstrated an efficient HEV‐dependent restriction in JEG‐3. Conclusion: We showed differential tissue‐specific host responses to HEV genotypes, adding to our understanding of the mechanisms contributing to fatal outcomes of HEV infections during pregnancy. Using this cell‐culture system, new therapeutic options for HEV during pregnancy can be identified and evaluated. (Hepatology Communications 2018;2:173–187)
Synthesis of Linear ABC Triblock Copolymers and Their Self‐Assembly in Solution
Authors: Konishcheva Evgeniia , Daubian Davy , Gaitzsch Jens , Meier Wolfgang
Published: January 2018

The self‐assembly of amphiphilic block copolymers has attracted the interest of a large number of research groups in the past two decades. Many examples have been reported using AB diblock copolymers, but the self‐assembly becomes more complex and shows a greater variety if ABC triblock copolymers are used. However, the synthesis of the polymer becomes more demanding since end‐group modifications or chain extensions become necessary. Using various kinds of polymerization techniques, pure triblock copolymers have been reported and their synthesis is covered in this review. Following the synthesis, a detailed and thorough analysis of the self‐assembly behaviour is the next step. We have selected promising and well characterized examples to show the range of self‐assembled structures possible, covering novel shapes of micelles but also polymersomes with an asymmetric membrane. Our selection of current examples in literature show the challenges and chances associated with amphiphilic ABC triblock copolymers.
The future of interpersonal skills development: Immersive virtual reality training with virtual humans
Authors: Schmid Mast Marianne , Kleinlogel Emmanuelle P. , Tur Benjamin , Bachmann Manuel
Published: January 2018

We present how immersive virtual reality (IVR) technology can be used for interpersonal skills training in organizations. We review the distinguishing features of IVR and its potential strengths and limitations for interpersonal skills training. There is a pressing need for more empirical evidence, which is why we propose a research agenda with the aim of establishing IVR interpersonal skills training in the domain of human resource development. The proposed research agenda encompasses a set of 10 hypotheses that cover two axes: (a) factors that affect training transfer and (b) personality characteristics. We illustrate how these hypotheses can be tested empirically and discuss limitations and future roles for HRD scholars in such research.
A decision analytic model for prevention of hepatitis B virus infection in Sub‐Saharan Africa using birth‐dose vaccination
Authors: Anderson Sarah , Harper Lorie M. , Dionne‐Odom Jodie , Halle‐Ekane Gregory , Tita Alan T.N.
Published: January 2018

Objective

To compare prenatal maternal hepatitis B virus (HBV) screening and infant vaccination strategies to inform policy on HBV prevention in Sub‐Saharan Africa.

Methods

A decision analytic model was created using previously published data to assess the ability of three intervention strategies to prevent HBV infection by age 10 years. Strategy 1 comprised of universal vaccination with a pentavalent vaccine (HBV, diphtheria, tetanus, pertussis, and Haemophilus influenzae) at age 6 weeks. Strategy 2 comprised of universal HBV vaccine at birth plus pentavalent vaccine. Strategy 3 comprised of maternal prenatal HBV screening and targeted HBV vaccine at birth for all exposed infants plus pentavalent vaccine. The reference strategy provided neither maternal screening nor infant vaccination. Rates of HBV infection and costs were compared.

Results

The reference strategy had an HBV infection rate of 2360 per 10 000 children. The HBV infection rate for strategy 1 was 813 per 10 000 children vaccinated (1547 cases prevented). Strategies 2 and 3 prevented an additional 384 cases and 362 cases, respectively. Inclusion of HBV vaccination at birth was the preferred approach at a willingness‐to‐pay threshold of US$150.

Conclusion

Including a birth‐dose HBV vaccine in the standard schedule was both cost‐effective and prevented additional infections.
Marital commitment, communication and marital satisfaction: An analysis based on actor–partner interdependence model
Authors: Hou Yubo , Jiang Feng , Wang Xinrui
Published: January 2018

Marital commitment and satisfaction are known to be closely related, but only limited research has examined the asymmetric interaction patterns between spouses. In this paper, the authors study 400 Chinese couples and find that communication mediates the relationship between marital commitment and marital satisfaction. Using the actor–partner interdependence model, they find that wives and husbands show asymmetric associations for marital commitment, communication and satisfaction. Specifically, compared with husbands, wives are more attuned to the path from marital commitment to marital satisfaction via communication. Implications and limitations are discussed.
Assessing the Impacts of Climate Change on the Quantity and Quality of Agricultural Runoff (Case Study: Golgol River Basin)
Authors: Moshtaghi Bahman , Niksokhan Mohammad Hossein , Ghazban Fereydoun , Dalilsafaee Sepehr
Published: January 2018

The effects of climate change and global warming have become increasingly evident in recent years. Changes in climate may impact water availability, water needs for agriculture and agricultural runoff. The Golgol River Basin has been investigated to examine the effect of climate change. HadCM3 model output under the A2 emission scenario during the two periods of 2046–2065 and 2080–2099 is used to predict temperature and precipitation amount under climate change impact, while the LARS‐WG model is used for downscaling. SWAT was applied to simulate runoff, nitrate and organic nitrogen. The SWAT‐CUP and SUFI‐2 methods were used for calibration. Introducing downscaled results of AOGCM models into the hydrological model and assuming similar regional conditions including fertilizer and land use, the changes in runoff and pollutants in the future were also simulated. It was observed that during 2046–2065, the average monthly runoff, nitrate and organic nitrogen loads would decrease by 27, 18 and 13.5%. The 2080–2099 period when compared to the present shows that the average monthly runoff, nitrate and organic nitrogen loads would decrease by 45, 33 and 35%. So according to runoff quality degradation, management solutions must be found to reduce pollutants. Copyright © 2018 John Wiley & Sons, Ltd.
Development and biocompatibility evaluation of biodegradable bacterial cellulose as a novel peripheral nerve scaffold
Authors: Hou Yuanjing , Wang Xinyu , Yang Jing , Zhu Rong , Zhang Zongrui , Li Yi
Published: January 2018

Peripheral nerve injury is a serious medical problem and severely affects normal life of patient. Bacterial cellulose (BC) is considered as a novel promising biomaterial for tissue engineering, but the poor biodegradability limits its application. In this study, biodegradable bacterial cellulose scaffolds were prepared with different oxidation degrees (O.Ds.) using sodium periodate, evaluating their potential application in peripheral nerve repair. The chemical structure and surface morphology of the oxidized bacterial cellulose (OBC) scaffolds were characterized using Fourier transform infrared spectroscopy, Wide angle X‐ray diffraction, and Scanning electron microscope. The porosity, mechanical properties, and degradation behavior of the OBC series scaffolds were extensively examined. Cellular viability and blood compatibility of OBC scaffolds were studied by MTT assay and hemolytic test using Schwann cells (SCs) and red blood cells (RBCs), respectively. The results demonstrated that the biodegradability of OBC scaffolds was improved significantly. OBC scaffolds with lower O.Ds. displayed high porosity with interconnected pores, suitable mechanical property, and biodegradability for peripheral nerve repair. In vitro cytotoxicity and hemolysis test analysis indicated that OBC0.05/3 scaffold is cellular and blood compatible, demonstrating its potential application as a good candidate for peripheral nerve repair. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1288–1298, 2018.
Instrumented indentation for determination of mechanical properties of human cornea after ultraviolet‐A crosslinking
Authors: Nohava Jiri , Swain Michael , Lang Stefan J. , Maier Philip , Heinzelmann Sonja , Reinhard Thomas , Eberwein Philipp
Published: January 2018

UVA crosslinking is used for treatment of corneal diseases such as keratoconus in order to stabilize the corneal tissue by crosslinking of the collagen fibers. It has been shown that the crosslinking treatment leads to a stiffening of the central corneal tissue. However, knowledge of lateral extent of the corneal stiffening as well as a systematic study of the mechanical response of human cornea is still missing. In our study we measured the stiffness (elastic modulus) of the anterior surface of healthy and crosslinked human corneas by instrumented indentation using a spherical indenter. The results show that the stiffness of the central and paracentral cornea increased almost two times after the crosslinking but the stiffening effect rapidly decreased towards the periphery of the radiation field. These new insights into the understanding of the biomechanical response of corneal crosslinking shall contribute to a better understanding and an optimization of this perspective medical treatment. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1413–1420, 2018.
Immunoisolating poly(ethylene glycol) based capsules support ovarian tissue survival to restore endocrine function
Authors: Day James R. , David Anu , Cichon Alexa L. , Kulkarni Tanay , Cascalho Marilia , Shikanov Ariella
Published: January 2018

A common irreversible adverse effect of life‐saving anticancer treatments is loss of gonadal endocrine function and fertility, calling for a need to focus on post‐treatment quality of life. Here, we investigated the use of poly(ethylene glycol)‐vinyl sulfone (PEG‐VS) based capsules to support syngeneic donor ovarian tissue for restoration of endocrine function in mice. We designed a dual immunoisolating capsule (PEG‐Dual) by tuning the physical properties of the PEG hydrogels and combining proteolytically degradable and nondegradable layers to meet the numerous requirements for encapsulation and immunoisolation of ovarian tissue, such as nutrient diffusion and tissue expansion. Tuning the components of the PEG‐Dual capsule to have similar physical properties allowed for concentric encapsulation. Upon implantation, the PEG‐based capsules supported ovarian tissue survival and led to a significant decrease in follicle stimulating hormone levels 60 days postimplantation. Mice that received the implants resumed regular estrous cycle activity and follicle development in the implanted grafts. The PEG‐Dual capsule provided an environment conducive for tissue survival, while providing a barrier to the host environment. This study demonstrated for the first time that immunoisolating PEG‐VS capsules can support ovarian follicular development resulting in the restoration of ovarian endocrine function and can be applied to future allogeneic studies. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1381–1389, 2018.
MiR‐548a‐3p regulates inflammatory response via TLR4/NF‐κB signaling pathway in rheumatoid arthritis
Authors: Wang Yingliang , Zheng Feng , Gao Guohong , Yan Shushan , Zhang Laixia , Wang Li , Cai Xiao , Wang Xiaodong , Xu Donghua , Wang Jibo
Published: January 2018

Currently published studies have implicated that microRNAs (miRNAs) including exosomes‐encapsulated miRNAs play a critical role in rheumatoid arthritis (RA). Previously, we have found that exosomes‐encapsulated miR‐548a‐3p was significantly decreased in serum samples from RA patients by miRNAs microarray analysis. However, little is known of the role of miR‐548a‐3p in the development and progression of RA. In this study, we aim to investigate the underlying molecular mechanisms of miR‐548a‐3p in RA, which will provide new insight into understanding the pathogenesis of RA and identifying novel therapeutics targets for this disease. As validated by quantitative real‐time polymerase chain reaction (qRT‐PCR), the expression of miR‐548a‐3p in serum exosomes and peripheral blood mononuclear cells (PBMCs) of RA patients (n = 76) was obviously down‐regulated compared with healthy controls (n = 20). Serum exosomal miR‐548a‐3p was negatively associated with levels of CRP, RF, and ESR in serum of patients with RA. MiR‐548a‐3p could inhibit the proliferation and activation of pTHP‐1 cells by regulating the TLR4/NF‐κB signaling pathway. Accordingly, exosomes‐delivered miR‐548a‐3p may be a critical factor predicting the disease activity of RA. MiR‐548a‐3p/TLR4/NF‐κB axis can serve as promising targets for RA diagnosis and treatment.
Testican‐1, as a novel diagnosis of sepsis
Authors: Lee Yuri , Lee Wonhwa , Chang Hyun‐Ha , Kim Shin‐Woo , Kim Jaehong , Bae Jong‐Sup
Published: January 2018

The development of new sepsis‐specific biomarkers is mandatory to improve the detection and monitoring of the disease. Testican‐1 is a highly conserved, multidomain proteoglycan that is most prominently expressed in the thalamus of the brain, and is upregulated in activated astroglial cells of the cerebrum. The aim of this study was to evaluate blood levels of Testican‐1 in septic patients. A prospective study of 82 patients with sepsis was conducted. Furthermore, C57BL/6 mice were administrated with lipopolysaccharide (LPS), high mobility group box 1 (HMGB1) protein or subjected to cecal ligation and puncture (CLP) surgery. Alternatively, human umbilical vein endothelial cells (HUVECs) or C57BL/6 mice were exposed to LPS (100 ng/mL) or HMGB1 (1 μg/mL). LPS, HMGB1, or CLP enhanced the synthesis and secretion of Testican‐1 in HUVECs and mice. In patients admitted to the intensive care unit (ICU) with sepsis, circulating levels of Testican‐1 were significantly high (sepsis, 20.44‐63.37 ng/mL, n = 30; severe sepsis, 41.30‐98.69 ng/mL, n = 22; septic shock, 98.10‐151.85 ng/mL, n = 30) when compared to the levels of control donors (6.97‐8.77 ng/mL, n = 21), reflecting the severity of the disease. These results suggest that in septic patients, Testican‐1 blood level is related to the severity of sepsis and Testican‐1 could be used as a biomarker to determine the severity of sepsis.
Synthesis and Characterization of a New Organic–Inorganic Hybrid Hydrogel by Using SiO2 Nanoparticles as an Initiator
Authors: Wei Xinfang , Wang Haiwang , Bian Jiali , Xu Hongyu , Wu Jiajie , Deng Yuan , Ma Zhiyu , Wang Bingzhu , Zhu Ying , Ye Li , Xu Xin , Liu Wenge , Qi Xiwei
Published: January 2018

A new type of organic–inorganic hybrid hydrogel (OIHH) was prepared under low air pressure using SiO2 nanoparticles as initiator. The obtained OIHH shows a novel microstructure and characteristics, which increased the salt resistance and water absorbance. We investigate the effects of the reaction conditions on the absorption ability. The xerogel shows absorbance of 339.9 and 102.8 g/g for distilled water and for 0.9 wt% NaCl solution. Moreover, a reasonable microstructure of the superabsorbent polymer is shown.
MicroRNA‐22 suppresses cell proliferation, migration and invasion in oral squamous cell carcinoma by targeting NLRP3
Authors: Feng Xiaodong , Luo Qingqiong , Wang Han , Zhang Han , Chen Fuxiang
Published: January 2018

MicroRNAs (miRNAs) have been implicated as important regulators of carcinogenesis and tumor development. Recently, microRNA‐22 (miR‐22) has been reported to be a cancer‐related miRNA in several types of tumors. In this study, we aimed to investigate the role of miR‐22 in oral squamous cell carcinoma (OSCC). We found that miR‐22 expression was significantly decreased in OSCC tissues compared with that in the adjacent noncancerous tissues. Furthermore, lentivirus‐mediated miR‐22 overexpression markedly reduced OSCC cell viability, migration and invasion, whereas miR‐22 inhibitor promoted these parameters. Mechanistically, NLR family pyrin domain containing three (NLRP3) was identified as a direct target of miR‐22. miR‐22 expression was inversely correlated with NLRP3 expression both in OSCC tissues and cell lines. Moreover, overexpression of miR‐22 in OSCC cells could reverse the tumor‐promoting effect of the activated NLRP3 inflammasome and vice versus. Therefore, our results indicate that miR‐22 may play a suppressive role in OSCC by targeting NLRP3, which offer new insights into the molecular mechanisms of the growth and metastasis of OSCC.
Long non‐coding RNA TCONS_00041960 enhances osteogenesis and inhibits adipogenesis of rat bone marrow mesenchymal stem cell by targeting miR‐204‐5p and miR‐125a‐3p
Authors: Shang Guowei , Wang Yadong , Xu Yan , Zhang Shanfeng , Sun Xiaoya , Guan Hongya , Zhao Xuefeng , Wang Yisheng , Li Yuebai , Zhao Guoqiang
Published: January 2018

A growing number of long non‐coding RNAs (lncRNAs) have been found to be involved in diverse biological processes such as cell cycle regulation, embryonic development, and cell differentiation. However, limited knowledge is available concerning the underlying mechanisms of lncRNA functions. In this study, we found down‐regulation of TCONS_00041960 during adipogenic and osteogenic differentiation of glucocorticoid‐treated bone marrow mesenchymal stem cells (BMSCs). Furthermore, up‐regulation of TCONS_00041960 promoted expression of osteogenic genes Runx2, osterix, and osteocalcin, and anti‐adipogenic gene glucocorticoid‐induced leucine zipper (GILZ). Conversely, expression of adipocyte‐specific markers was decreased in the presence of over‐expressed TCONS_00041960. Mechanistically, we determined that TCONS_00041960 as a competing endogenous RNA interacted with miR‐204‐5p and miR‐125a‐3p to regulate Runx2 and GILZ, respectively. Overall, we identified a new TCONS_00041960‐miR‐204‐5p/miR‐125a‐3p‐Runx2/GILZ axis involved in regulation of adipogenic and osteogenic differentiation of glucocorticoid‐treated BMSCs.
Microvesicles: Intercellular messengers in cutaneous wound healing
Authors: Laberge Alexandra , Arif Syrine , Moulin Véronique J.
Published: January 2018

Longtime considered as inert cellular debris, microvesicles (MVs) have gained tremendous attention in the past decade. MVs are 100–1000 nm vesicles released into the extracellular environment by the outward budding and fission of the plasma membrane. They are now regarded as essential mediators of cell‐to‐cell interactions in a variety of physiological and pathological processes. In this review, we discuss the increasingly recognized contribution of MVs to the biology of wound healing. We highlight current concepts relating to the biogenesis and mode of action of MVs. We discuss the emerging roles of MVs in the hemostatic, inflammatory, proliferative, and remodeling phases of the injury‐repair response. In doing so, we provide a new perspective on the dynamics of intercellular communication involved in skin homeostasis.
Effect of restriction vegan diet's on muscle mass, oxidative status, and myocytes differentiation: A pilot study
Authors: Vanacore Daniela , Messina Giovanni , Lama Stefania , Bitti Giuseppe , Ambrosio Pasqualina , Tenore Giancarlo , Messina Antonietta , Monda Vincenzo , Zappavigna Silvia , Boccellino Mariarosaria , Novellino Ettore , Monda Marcellino , Stiuso Paola
Published: January 2018

This study was conceived to evaluate the effects of three different diets on body composition, metabolic parameters, and serum oxidative status. We enrolled three groups of healthy men (omnivores, vegetarians, and vegans) with similar age, weight and BMI, and we observed a significant decrease in muscle mass index and lean body mass in vegan compared to vegetarian and omnivore groups, and higher serum homocysteine levels in vegetarians and vegans compared to omnivores. We studied whether serum from omnivore, vegetarian, and vegan subjects affected oxidative stress, growth and differentiation of both cardiomyoblast cell line H9c2 and H‐H9c2 (H9c2 treated with H2O2 to induce oxidative damage). We demonstrated that vegan sera treatment of both H9c2 and H‐H9c2 cells induced an increase of TBARS values and cell death and a decrease of free NO2− compared to vegetarian and omnivorous sera. Afterwards, we investigated the protective effects of vegan, vegetarian, and omnivore sera on the morphological changes induced by H2O2 in H9c2 cell line. We showed that the omnivorous sera had major antioxidant and differentiation properties compared to vegetarian and vegan sera. Finally, we evaluated the influence of the three different groups of sera on MAPKs pathway and our data suggested that ERK expression increased in H‐H9c2 cells treated with vegetarian and vegan sera and could promote cell death. The results obtained in this study demonstrated that restrictive vegan diet could not prevent the onset of metabolic and cardiovascular diseases nor protect by oxidative damage.
miR‐181b‐induced SMAD7 downregulation controls granulosa cell apoptosis through TGF‐β signaling by interacting with the TGFBR1 promoter
Authors: Yao Wang , Pan Zengxiang , Du Xing , Zhang Jinbi , Li Qifa
Published: January 2018

SMAD7 disrupts the TGF‐β signaling pathway by influencing TGFBR1 stability and by blocking the binding of TGFBR1 to SMAD2/3. In this study, we showed that SMAD7 attenuated the TGF‐β signaling pathway in ovarian granulosa cells (GCs) by regulating TGFBR1 transcriptional activity. To function as a transcription factor, SMAD7 downregulated the mRNA levels of TGFBR1 via direct binding to the SMAD‐binding elements (SBEs) within the promoter region of pig TGFBR1. We also showed that SMAD7 enhanced porcine GC apoptosis by interrupting TGFBR1 and the TGF‐β signaling pathway. Interestingly, miR‐181b, a microRNA that is downregulated during porcine follicular atresia, was identified to be directly targeting SMAD7 at its 3′‐UTR. By inhibiting SMAD7, miR‐181b could inhibit GC apoptosis by activating the TGF‐β signaling pathway. Our findings provide new insights into the mechanisms underlying the regulation of the TGF‐β signaling pathway by SMAD7 and miR‐181b.
Antibody‐drug conjugates: Promising and efficient tools for targeted cancer therapy
Authors: Nasiri Hadi , Valedkarimi Zahra , Aghebati‐Maleki Leili , Majidi Jafar
Published: January 2018

Over the recent decades, the use of antibody–drug conjugates (ADCs) has led to a paradigm shift in cancer chemotherapy. Antibody–based treatment of various human tumors has presented dramatic efficacy and is now one of the most promising strategies used for targeted therapy of patients with a variety of malignancies, including hematological cancers and solid tumors. Monoclonal antibodies (mAbs) are able to selectively deliver cytotoxic drugs to tumor cells, which express specific antigens on their surface, and has been suggested as a novel category of agents for use in the development of anticancer targeted therapies. In contrast to conventional treatments that cause damage to healthy tissues, ADCs use mAbs to specifically attach to antigens on the surface of target cells and deliver their cytotoxic payloads. The therapeutic success of future ADCs depends on closely choosing the target antigen, increasing the potency of the cytotoxic cargo, improving the properties of the linker, and reducing drug resistance. If appropriate solutions are presented to address these issues, ADCs will play a more important role in the development of targeted therapeutics against cancer in the next years. We review the design of ADCs, and focus on how ADCs can be exploited to overcome multiple drug resistance (MDR).
Cell tracking, survival, and differentiation capacity of adipose‐derived stem cells after engraftment in rat tissue
Authors: Muñoz Mario F. , Argüelles Sandro , Guzman‐Chozas Matias , Guillén‐Sanz Remedios , Franco Jaime M. , Pintor‐Toro José A. , Cano Mercedes , Ayala Antonio
Published: January 2018

Adipose tissue is an important source of adipose derived stem cells (ADSCs). These cells have the potential of being used for certain therapies, in which the main objective is to recover the function of a tissue/organ affected by a disease. In order to contribute to repair of the tissue, these cells should be able to survive and carry out their functions in unfavorable conditions after being transplanted. This process requires a better understanding of the biology involved: such as the time cells remain in the implant site, how long they stay there, and whether or not they differentiate into host tissue cells. This report focuses on these questions. ADSC were injected into three different tissues (substantia nigra, ventricle, liver) and they were tracked in vivo with a dual GFP‐Luc reporter system. The results show that ADSCs were able to survive up to 4 months after the engraftment and some of them started showing resident cell tissue phenotype. These results demonstrate their long‐term capacity of survival and differentiation when injected in vivo.
Chronic high glucose and insulin stimulate bone‐marrow stromal cells adipogenic differentiation in young spontaneously hypertensive rats
Authors: Chaves Neto Antonio H. , Brito Victor G. B. , Landim de Barros Thamine , do Amaral Caril C. F. , Sumida Dóris H. , Oliveira Sandra H. P.
Published: January 2018

We evaluated whether genetic predisposition is sufficient to induce changes due to chronic high glucose (HG; 25 mmol/L) in the presence or absence of insulin (HGI; 10 μg/ml) on osteogenic differentiation and markers in bone‐marrow mesenchymal stem cells (BMSCs) from young Wistar (WBMSCs) and spontaneous hypertensive rats (SBMSCs) without hypertension. HG suppressed osteogenic differentiation in both the strains, observed by mineralization inhibition and decreased levels of the osteogenic markers Runx2, osterix, osteopontin, and bone sialoprotein, compared to osteogenic medium (OM) cells. In WBMSCs, the effects of HG were associated with the down regulation of ERK1/2 and up regulation of p38 activities; however, HGI did not revert the effects of HG on MAPK activities. Moreover, HG did not affect MAPK signaling in SBMSCs compared to that in OM. HGI increased mineralization in WBMSCs compared to that in OM, but not in SBMSCs. High expression of peroxisome proliferator‐activated receptor‐gamma and glucose transporter type 4 in OM could be related with the predisposition to adipogenic differentiation noted in SBMSCs and was confirmed by emergence of adipocyte‐like cells by HGI treatment. Downregulation of p38 and upregulation of JNK activities were observed in both BMSCs treated with HGI compared to those treated by HG. Ma (osmotic control) also suppressed osteogenic differentiation in both the strains. In conclusion, we demonstrated that SBMSCs from young spontaneous hypertensive rats, without hypertension but with genetic and epigenetic predisposition, exhibited decreased osteoblastic differentiation under HG and HGI did not revert the effects of HG in SBMSCs but increased adipogenic differentiation.
Circulating monocyte chemoattractant protein‐1 (MCP‐1) is associated with cachexia in treatment‐naïve pancreatic cancer patients
Authors: Talbert Erin E. , Lewis Heather L. , Farren Matthew R. , Ramsey Mitchell L. , Chakedis Jeffery M. , Rajasekera Priyani , Haverick Ericka , Sarna Angela , Bloomston Mark , Pawlik Timothy M. , Zimmers Teresa A. , Lesinski Gregory B. , Hart Phil A. , Dillhoff Mary E. , Schmidt Carl R. , Guttridge Denis C.
Published: January 2018

Background

Cancer‐associated wasting, termed cancer cachexia, has a profound effect on the morbidity and mortality of cancer patients but remains difficult to recognize and diagnose. While increases in circulating levels of a number of inflammatory cytokines have been associated with cancer cachexia, these associations were generally made in patients with advanced disease and thus may be associated with disease progression rather than directly with the cachexia syndrome. Thus, we sought to assess potential biomarkers of cancer‐induced cachexia in patients with earlier stages of disease.

Methods

A custom multiplex array was used to measure circulating levels of 25 soluble factors from 70 pancreatic cancer patients undergoing attempted tumour resections. A high‐sensitivity multiplex was used for increased sensitivity for nine cytokines.

Results

Resectable pancreatic cancer patients with cachexia had low levels of canonical pro‐inflammatory cytokines including interleukin‐6 (IL‐6), interleukin‐1β (IL‐1β), interferon‐γ (IFN‐γ), and tumour necrosis factor (TNF). Even in our more sensitive analysis, these cytokines were not associated with cancer cachexia. Of the 25 circulating factors tested, only monocyte chemoattractant protein‐1 (MCP‐1) was increased in treatment‐naïve cachectic patients compared with weight stable patients and identified as a potential biomarker for cancer cachexia. Although circulating levels of leptin and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) were found to be decreased in the same cohort of treatment‐naïve cachectic patients, these factors were closely associated with body mass index, limiting their utility as cancer cachexia biomarkers.

Conclusions

Unlike in advanced disease, it is possible that cachexia in patients with resectable pancreatic cancer is not associated with high levels of classical markers of systemic inflammation. However, cachectic, treatment‐naïve patients have higher levels of MCP‐1, suggesting that MCP‐1 may be useful as a biomarker of cancer cachexia.
Fluid dynamic characterization of a fluidized‐bed perfusion bioreactor with CFD–DEM simulation
Authors: Huang Zheqing , Odeleye Akinlolu Oyekunle Oluseun , Ye Hua , Cui Zhanfeng , Yang Aidong
Published: January 2018

BACKGROUND

In the recent development of regenerative medicine, the low yields of progenitor cells have limited the large‐scale clinical applications. To overcome the limitation, a novel fluidized bed bioreactor has emerged. However, a detailed understanding of its fluid dynamics is still lacking.

RESULTS

A 3D modeling approach that couples computational fluid dynamics (CFD) and a discrete element method (DEM) was used to simulate the liquid and solid flows in a bioreactor being designed for stem cells expansion. The model was validated by comparing the simulation results with literature experimental data [Chem Eng Sci 60:1889–1900 (2005)], which showed a good agreement. Using the validated model, the effects of the superficial liquid velocity, particle size and particle density on the solids volume fraction, shear stress on the particles and liquid–solid mass transfer coefficient of dissolved oxygen and glucose were analyzed.

CONCLUSIONS

Simulation results show that particle size and density have an important impact on the shear stress distribution, and that the liquid velocity affects the shear stress distribution rather modestly when its value is beyond the minimum fluidization velocity. The liquid–particle mass transfer coefficient of dissolved oxygen and glucose can be improved by raising the liquid velocity, and the adoption of a high‐density material allows the reactor to operate with higher liquid velocities before reaching shear stress heterogeneities. Furthermore, the two objectives, (i) maintaining lower and homogeneously distributed shear stress and (ii) improving mass transfer, pose conflicting requirements on certain design parameters which need to be carefully considered in the reactor design. © 2018 Society of Chemical Industry
Amyloid goiter mimicking subacute thyroiditis on clinical and imaging findings: A case report
Authors: Lee Yoo Jin , Jung Soo Jin , Kim Dong Wook , Cho Hwa Jin , Ahn Ki Jung
Published: January 2018

Amyloid goiter (AG) is defined as the diffuse enlargement of the thyroid gland resulting from extensive amyloid deposition. Imaging findings in AG may vary depending on the amount of amyloid and fat deposition. A few case reports of AG with clinically subacute thyroiditis (SAT)‐like syndrome have been published. However, there have been no reports on AG mimicking SAT with clinical and imaging findings. Herein, we present a case of AG mimicking SAT with a detailed report of the clinical and imaging findings.
Prenatal sonographic diagnosis of a vitelline vein aneurysm
Authors: Sahinoglu Zeki , Cetinkaya Burcu
Published: January 2018

We report a case of vitelline vein aneurysm detected at 23 weeks of gestation. Few postnatal cases of vitelline vein aneurysm have been reported; however, due to their similar appearances most of them were considered initially as umbilical vein dilatations. The accurate prenatal diagnosis of vitelline vein aneurysm and early postnatal surgical treatment are crucial steps to prevent postnatal obliterative extension of thrombosis that might cause severe neonatal morbidity.
The learning curve in diagnosing acute appendicitis with emergency sonography among novice emergency medicine residents
Authors: Kim Jeehyun , Kim Kipum , Kim Jungwan , Yoo Jungwoo , Jeong Wonjoon , Cho Sunguk , Joo Kihyuk , Cho Yongchul , Lee Jinwoong , Ryu Seung , Yoo Yeonho
Published: January 2018

Purpose

Ultrasonography (US) has good accuracy for diagnosing appendicitis when it is performed by emergency physicians. This study aimed to determine the amount of experience that is required to achieve competency in this field.

Methods

Three novice emergency medicine residents completed a 1‐day training course regarding the US diagnosis of appendicitis. Then, they performed appendix US in the emergency department on patients complaining of right lower quadrant pain. All included patients also underwent computed tomography or US performed by a board‐certified radiologist, to confirm the emergency US diagnosis. The agreement between the diagnoses of novices and experts was evaluated.

Results

A total of 266 patients were included, and the overall Cohen's kappa coefficient was 0.77 (95% confidence interval [CI]: 0.69‐0.84). The kappa value of first 20 cases was 0.49 (95% CI: 0.27‐0.71). It increased rapidly during evaluation of the first 20 cases. After the first 20 cases, the kappa coefficient was 0.84 (95% CI: 0.77‐0.92). The sensitivity and specificity values for the first 20 cases were 64.3% (95% CI: 77.6%‐90.7%) and 84.4% (95% CI: 85.4%‐95.4%), respectively. After the first 20 cases, the sensitivity and specificity values increased to 90.9% (95% CI: 83.4%‐95.8%) and 93.5% (95% CI: 87.0%‐97.3%), respectively.

Conclusions

A minimum of 20 cases are needed to achieve competency in emergency US diagnosis of acute appendicitis.
Synthesis of New Pyrimido[5′,4′:5,6][1,4]thiazino[2,3‐b]quinoxaline Derivatives in One Step
Authors: Karimian Azam
Published: January 2018

As a continuation of our search for new heterocyclic compounds, the synthesis of pyrimido[5′,4′:5,6][1,4]thiazino[2,3‐b]quinoxaline ring system is described. A series of new derivatives of this heterocyclic system (3a–d) have been synthesized through the one‐pot heterocyclization of the appropriate 5‐amino6‐methylpyrimidine‐4‐thiols and 2,3‐dichloroquinoxaline in the presence of K2CO3 in dimethylformamide under reflux. N‐alkylation of the synthesized compounds with alkyl halides in KOH/dimethylformamide also gave the desired new derivatives of N‐alkylated pyrimido[5′,4′:5,6][1,4]thiazino[2,3‐b]quinoxalines (4a–h). All the synthesized products were characterized and confirmed by their spectroscopic and microanalytical data.
Youth Livelihoods in the Cellphone Era: Perspectives from Urban Africa
Authors: Porter Gina , Hampshire Kate , de Lannoy Ariane , Bango Andisiwe , Munthali Alister , Robson Elsbeth , Tanle Augustine , Abane Albert , Owusu Samuel
Published: January 2018

Issues surrounding youth employment and unemployment are central to the next development decade. Understanding how youth use mobile phones as a means of communicating and exchanging information about employment and livelihoods is particularly important given the prominence of mobile phone use in young lives. This paper explores and reflects on youth phone usage in Ghana, Malawi and South Africa, drawing on mixed‐methods research with young people aged approximately 9–25 years, in 12 (high density) urban and peri‐urban sites. Comparative work across these sites offers evidence of both positive and negative impacts. The final section of the paper considers policy implications. © 2018 The Authors Journal of International Development Published by John Wiley & Sons Ltd.
The N-terminal peptide moiety of the Mycobacterium tuberculosis 19 kDa lipoprotein harbors RP105-agonistic properties
Authors: Schultz Thomas E , Wiesmüller Karl-Heinz , Lucas Megan , Dobos Karen M , Baxter Alan G , Blumenthal Antje
Published: January 2018

Radioprotective 105 kDa (RP105, CD180) is a member of the Toll-like receptor (TLR) family that interacts with TLR2 and facilitates recognition of mature lipoproteins expressed by Mycobacterium tuberculosis and Mycobacterium bovis BCG. In this study, we used synthetic lipopeptide analogs of the M. tuberculosis 19 kDa lipoprotein to define structural characteristics that promote RP105-mediated host cell responses. A tripalmitoylated lipopeptide composed of the first 16 N-terminal amino acids of the M. tuberculosis 19 kDa lipoprotein induced RP105-dependent TNF and IL-6 production by macrophages. Di- and tripalmitoylated variants of this lipopeptide elicited an equivalent RP105-dependent response, indicating that while the lipid moiety is required for macrophage activation, it is not a determinant of RP105 dependency. Instead, substitution of two polar threonine residues at positions 7 and 8 with nonpolar alanine residues resulted in reduced RP105 dependency. These results strongly suggest that the amino acid composition of the M. tuberculosis 19 kDa lipoprotein, and likely other mycobacterial lipoproteins, is a key determinant of RP105 agonism.
Characterization of unusual DS‐1‐like G3P[8] rotavirus strains in children with diarrhea in Japan
Authors: Komoto Satoshi , Ide Tomihiko , Negoro Manami , Tanaka Takaaki , Asada Kazutoyo , Umemoto Masakazu , Kuroki Haruo , Ito Hiroaki , Tanaka Shigeki , Ito Mitsue , Fukuda Saori , Suga Shigeru , Kamiya Hajime , Nakano Takashi , Taniguchi Koki
Published: January 2018

The emergence and rapid spread of novel DS‐1‐like intergenogroup reassortant rotaviruses having the equine‐like G3 genotype (DS‐1‐like G3P[8] strains) have been recently reported from several countries. During rotavirus surveillance in Japan in 2015–2016, three DS‐1‐like G3P[8] strains were identified from children with severe diarrhea. In the present study, we sequenced and characterized the full genomes of these three strains. On full‐genomic analysis, all three strains showed a unique genotype constellation including both genogroup 1 and 2 genes: G3‐P[8]‐I2‐R2‐C2‐M2‐A2‐N2‐T2‐E2‐H2. Phylogenetic analysis revealed that each of the 11 genes of the three strains was closely related to that of Japanese DS‐1‐like G1P[8] and/or Japanese equine‐like G3P[4] human strains. Thus, the three study strains were suggested to be reassortants that acquired the G3‐VP7 gene from equine G3 rotaviruses on the genetic background of DS‐1‐like G1P[8] strains. Our observations will provide important insights into the evolutionary dynamics of emerging DS‐1‐like G3P[8] strains.
Molecular epidemiology and genotype distributions of noroviruses and sapoviruses in Thailand 2000‐2016: A review
Authors: Kumthip Kattareeya , Khamrin Pattara , Maneekarn Niwat
Published: January 2018

Norovirus (NoV) and sapovirus (SaV) infections remain public health problems in Thailand, particularly, causing an acute gastroenteritis in people of all age groups. This review summarizes the epidemiology and genotype distribution of NoV and SaV in Thailand during the period of 2000‐2016. The overall prevalence of NoV infection in patients with acute gastroenteritis of all age groups ranged from 0.09% to 44.7% while those of SaV were 0.0‐15.0%. The majority of NoV genogroup detected was NoV GII with a small proportion of NoV GI. The NoV GII.4 was the most predominant genotype (63.4%) followed by GII.3 (15.0%), GII.6 (3.9%), GII.17 (3.3%), GII.13 (2.1%) and many other genotypes with small proportion. Furthermore, eight GII.4 variant strains and 11 different NoV recombinant strains had also been reported. For SaV, 10 different human SaV genotypes were detected including GI.1, GI.2, GI.4, GI.5, GII.1, GII.2, GII.3, GII.4, GIV.1, and GV.1.
Virological patterns of HCV patients with failure to interferon‐free regimens
Authors: Starace Mario , Minichini Carmine , De Pascalis Stefania , Macera Margherita , Occhiello Laura , Messina Vincenzo , Sangiovanni Vincenzo , Adinolfi Luigi E. , Claar Ernesto , Precone Davide , Stornaiuolo Gianfranca , Stanzione Maria , Ascione Tiziana , Caroprese Mara , Zampino Rosa , Parrilli Gianpaolo , Gentile Ivan , Brancaccio Giuseppina , Iovinella Vincenzo , Martini Salvatore , Masarone Mario , Fontanella Luca , Masiello Addolorata , Sagnelli Evangelista , Punzi Rodolfo , Salomone Megna Angelo , Santoro Renato , Gaeta Giovanni B. , Coppola Nicola
Published: January 2018

The study characterized the virological patterns and the resistance‐associated substitutions (RASs) in patients with failure to IFN‐free regimens enrolled in the real‐life setting. All 87 consecutive HCV patients with failed IFN‐free regimens, observed at the laboratory of the University of Campania, were enrolled. All patients had been treated with DAA regimens according to the HCV genotype, international guidelines, and local availability. Sanger sequencing of NS3, NS5A, and NS5B regions was performed at failure by home‐made protocols. Of the 87 patients enrolled, 13 (14.9%) showed a misclassified HCV genotype, probably causing DAA failure, 16 had been treated with a sub‐optimal DAA regimen, 19 with a simeprevir‐based regimen and 39 with an optimal DAA regimen. A major RAS was identified more frequently in the simeprevir regimen group (68.4%) and in the optimal regimen group (74.4%) than in the sub‐optimal regimen group (56.3%). The prevalence of RASs in NS3 was similar in the three groups (30.8‐57.9%), that in NS5A higher in the optimal regimen group (71.8%) than in the sub‐optimal regimen group (12.5%, P < 0.0001) and in the simeprevir regimen group (31.6%, P < 0.0005), and that in NS5B low in all groups (0‐25%). RASs in two or more HCV regions were more frequently identified in the optimal regimen group (46.6%) than in the simeprevir‐based regimen group (31.6%) and sub‐optimal regimen group (18.7%). In our real‐life population the prevalence of RASs was high, especially in NS3 and NS5A and in those treated with suitable DAA regimens.
Comparison of the digene hybrid capture 2 and Roche cobas 4800 HPV tests for detection of CIN2+ in a referral population in Japan
Authors: Sasagawa Toshiyuki , Maehama Toshiyuki , Osaka Yasuhiro , Sakamoto Jinichi , Shibata Takeo , Fujita Satoko , Takakura Masahiro , Takagi Hiroaki
Published: January 2018

To examine validity of the hybrid capture‐2 and cobas 4800 HPV tests, 396 women including 188 women visiting for cancer screening, and 208 referral cases were examined with both HPV tests and the liquid‐based cervical Pap test. Concordant results between the HPV assays were observed in 333 cases (coincident rates; 84.1%, kappa value; 0.682). The sensitivity for CIN2+ was 98.6% (69/70) and 82.9% (58/70) for HC2 and cobas 4800 (McNemar's test; P = 0.0026). The sensitivity for CIN3+ was 97.2% (35/36) and 83.3% (30/36) (Not significant, P = 0.0736). The specificities for CIN2+ or CIN3+ did not differ between the tests. The HPV16, 52, 18, 31, and 58 were the most common types in CIN2+ cases. Reasonable sensitivity for HPV52, and cross‐hybridization with some probable high‐risk HPV type such as HPV82 explain the higher sensitivity of HC2 than cobas 4800 in detection of CIN2+ in a referral population in Japan.
The antimalarial drug amodiaquine possesses anti‐ZIKA virus activities
Authors: Han Yingshan , Mesplède Thibault , Xu Hongtao , Quan Yudong , Wainberg Mark A.
Published: January 2018

Zika virus (ZIKV) outbreak has emerged as a global health threat, particularly in tropical areas, over the past few years. No antiviral therapy or vaccine is available at present. For these reasons, repurposing clinically approved drugs against ZIKV infection may provide rapid and cost‐effective global health benefits. Here, we explored this strategy and screened eight FDA‐approved drugs for antiviral activity against ZIKV using a cell‐based assay. Our results show that the antimalarial drug amodiaquine has anti‐ZIKV activity with EC50 at low micromolar concentrations in cell culture. We further characterized amodiaquine antiviral activity against ZIKV and found that it targets early events of the viral replication cycle. Altogether, our results suggest that amodiaquine may be efficacious for the treatment of ZIKV infection.
Investigation of gate induced noise in E‐mode GaN MOS‐HEMT and its effect on noise parameters
Authors: Panda D.K. , Lenka T.R.
Published: January 2018

In this paper, the effects of gate induced noise for a gate recessed enhancement‐mode GaN‐based metal‐oxide‐semiconductor high electron mobility transistor (MOS‐HEMT) is investigated. To analyze this, a surface potential–based compact model for gate induced noise is developed. The model is validated by comparing with TCAD device simulation results as well as with the available experimental data of GaN HEMT and MOS‐HEMT having different gate lengths and widths from the literature. With the help of the developed model, the effect of oxide thickness on different noise sources is investigated by considering all high‐frequency noise sources including the shot noise resulted from gate leakage current. The effects of gate leakage current on different technology dependent parameters such as oxide thickness and gate length are also investigated. A 2‐port noise equivalent circuit for GaN MOS‐HEMT is designed by considering all high‐frequency noise sources. The different noise parameter models are developed from the Y parameters of the 2‐port noise equivalent circuit and compared with available experimental data of GaN HEMT and MOS‐HEMT from literature. The impact of gate induced noise on all noise parameters is also investigated.