bluuebunny/crossref_metadata_2025_split huggingface dataset:
Necroptotic‐susceptible dendritic cells exhibit enhanced antitumor activities in mice
Authors: Zhao Zhanran , Zhang Guangzhi , Sun Yuefang , Winoto Astar 
Published: July 2020

AbstractIntroductionPriming of tumor‐specific T cells is a key to antitumor immune response and inflammation, in turn, is crucial for proper T‐cell activation. As antigen‐presenting cells can activate T cells, dendritic cells (DCs) loaded with tumor antigens have been used as immunotherapeutics against certain cancer in humans but their efficacy is modest. Necroptosis is a form of programmed cell death that results in the release of inflammatory contents. We previously generated mice with DC deficiency in a negative regulator of necroptosis, Fas‐associated death domain (FADD), and found that these mice suffer from systemic inflammation due to necroptotic DCs. We hypothesize that FADD‐deficient DCs could serve as a better vaccine than wild‐type (WT) DCs against tumors.Materials and MethodsFADD‐deficient and WT mouse DCs loaded with the relevant tumor peptide were injected onto mice before or after the syngeneic tumor challenge. DC vaccinations were repeated two more times and anti‐PD‐1 antibodies were coinjected in some experiments. Tumor sizes were measured by caliper, and the percentages of tumor‐free mice or mice survived were examined over time. The cytometric analysis was carried out to analyze various immune populations.ResultsIn two separate tumor models, we find that mice receiving FADD‐deficient DCs as vaccine rejected tumors significantly better than those receiving a WT DC vaccine. Tumor growth was severely hampered, and survival extended in these mice. More activated CD8 T cells together with elevated cytokines were observed in mice receiving the FADD‐deficient DC vaccine. Furthermore, we observed these effects were potent enough to protect against tumor challenge postinjection and can work in conjunction with anti‐PD‐1 antibodies to reduce the tumor growth.ConclusionsNecroptotic‐susceptible DCs are better antitumor vaccines than WT DCs in mice. Our findings suggest that necroptosis‐driven inflammation by DCs may be a novel avenue to generating a strong adaptive antitumor response in the clinical setting.
Stock market liberalization, foreign institutional investors, and informational efficiency of stock prices: Evidence from an emerging market
Authors: Li Yijie , Liu Jianghui , Wang Haizhi , Wang Peng 
Published: July 2020

AbstractThis study investigates the effects of investments by qualified foreign institutional investors (QFIIs) on the informational efficiency of stock prices in Chinese A‐share stock markets. Employing a large sample of listed firms from 2004 to 2012, we document a significant and positive relationship between stock price informativeness and stock ownership by foreign institutional investors. We also use the instrument‐variable approach, propensity‐score matching method, as well as an alternative measure of informational efficiency to ensure the robustness of our findings. We document that the effects of foreign ownership on informational efficiency is stronger for firms with lower levels of assets intangibility and in regions with less developed institutions. In addition, we document that the effects of foreign ownership on informational efficiency is more pronounced when QFIIs have better local information and more incentives to monitor.
In vitro and in silico genetic toxicity screening of flavor compounds and other ingredients in tobacco products with emphasis on ENDS
Authors: Hung Pei‐Hsuan , Savidge Matthew , De Mamata , Kang Jueichuan (Connie) , Healy Sheila M. , Valerio Luis G. 
Published: July 2020

AbstractElectronic nicotine delivery systems (ENDS) are regulated tobacco products and often contain flavor compounds. Given the concern of increased use and the appeal of ENDS by young people, evaluating the potential of flavors to induce DNA damage is important for health hazard identification. In this study, alternative methods were used as prioritization tools to study the genotoxic mode of action (MoA) of 150 flavor compounds. In particular, clastogen‐sensitive (γH2AX and p53) and aneugen‐sensitive (p‐H3 and polyploidy) biomarkers of DNA damage in human TK6 cells were aggregated through a supervised three‐pronged ensemble machine learning prediction model to prioritize chemicals based on genotoxicity. In addition, in silico quantitative structure‐activity relationship (QSAR) models were used to predict genotoxicity and carcinogenic potential. The in vitro assay identified 25 flavors as positive for genotoxicity: 15 clastogenic, eight aneugenic and two with a mixed MoA (clastogenic and aneugenic). Twenty‐three of these 25 flavors predicted to induce DNA damage in vitro are documented in public literature to be in e‐liquid or in the aerosols produced by ENDS products with youth‐appealing flavors and names. QSAR models predicted 46 (31%) of 150 compounds having at least one positive call for mutagenicity, clastogenicity or rodent carcinogenicity, 49 (33%) compounds were predicted negative for all three endpoints, and remaining compounds had no prediction call. The parallel use of these predictive technologies to elucidate MoAs for potential genetic damage, hold utility as a screening strategy. This study is the first high‐content and high‐throughput genotoxicity screening study with an emphasis on flavors in ENDS products.
A systematic review of microRNA expression studies with exposure to bisphenol A
Authors: Farahani Masoumeh , Rezaei‐Tavirani Mostafa , Arjmand Babak 
Published: July 2020

AbstractBisphenol A (BPA), as a common industrial component, is generally consumed in the synthesis of polymeric materials. To gain a deeper understanding of the detrimental effects of BPA, BPA‐induced microRNA (miRNA) alterations were investigated. A systematic search was performed in the PubMed, SCOPUS and Web of Science databases to evoke relevant published data up to August 10, 2019. We identified altered miRNAs that have been repeated in at least three studies. Moreover, miRNA homology analysis between human and nonhuman species was performed to determine the toxicity signatures of BPA in human exposure. In addition, to reflect the effects of environmental exposure levels of BPA, the study designs were categorized into two groups, including low and high doses according to the previous definitions. In total, 28 studies encountered our criteria and 17 miRNAs were identified that were differentially expressed in at least three independent studies. Upregulating miR‐146a and downregulating miR‐192, miR‐134, miR‐27b and miR‐324 were found in three studies. MiR‐122 and miR‐29a were upregulated in four studies after BPA exposure, and miR‐21 was upregulated in six studies. The results indicate that BPA at low‐level exposures can also alter miRNA expression in response to toxicity. Finally, the miRNA‐related pathways showed that BPA seriously can affect human health through various cell signaling pathways, which were predictable and consistent with existing studies. Overall, our findings suggest that further studies should be conducted to examine the role of miRNA level changes in human BPA exposure.
Mechanical performance and biocompatibility assessment of Zn‐0.05wt%Mg‐(0.5, 1 wt%) Ag alloys
Authors: Xiao Chi , Su Yun , Zhu Xiaoming , Yu Weiting , Cui Daping , Wei Xiaowei , Zhang Xiuzhi , Li Junlei , Wang Feng , Ren Yuping , Qin Gaowu , Zhao Dewei 
Published: July 2020

AbstractZn alloys are emerging as promising degradable biomedical materials due to their tailorable mechanical properties and moderate biodegradable rate, compared with conventional biodegradable metallic materials. Ag, as an effective antibacterial and reinforcing element, was incorporated into Zn‐0.05Mg alloys. In the present work, the effects of the Ag addition on mechanical, cytotoxic, hemolytic, pyrogenic, histological behaviors of the animal were investigated. The compressive yielding strength is enhanced from 198 MPa for Zn‐0.05Mg alloy up to 224 and 234 MPa for Zn‐0.05Mg‐0.5Ag and Zn‐0.05Mg‐1Ag alloys, respectively. When the compressive strain was 65%, the strength of the Zn‐0.05Mg‐1.0Ag alloy reached 833 MPa, which was much higher than that of 721 MPa for Zn‐0.05Mg alloy. The relative growth rate (RGR) for the extracts of Zn‐0.05Mg‐1Ag alloy with the concentrations of 10, 50, and 100% after 5 days incubation reaches 98.5, 95.2, and 94.2%, which are higher than those in extracts of Zn‐0.05Mg‐0.5Ag alloy (98.2, 93.9, 92.1%). The hemolysis rate of the Zn‐0.05Mg alloys with 0.5 and 1 wt% Ag is 2.46 and 2.28%, respectively. The variations of body weight and temperature, postinjection symptoms, pathological morphologies of the visceral organs demonstrate that the alloys are nontoxic according to the toxicity rating standards. Zn‐0.05wt%Mg‐(0.5, 1 wt%) Ag alloys are experimentally safe materials and promising for the future application as biodegradable medical devices.
Vitamin K2 Modulates Vitamin D‐Induced Mechanical Properties of Human 3D Bone Spheroids In Vitro
Authors: Schröder Maria , Riksen Elisabeth Aurstad , He Jianying , Skallerud Bjørn Helge , Møller Mona Elisabeth , Lian Aina‐Mari , Syversen Unni , Reseland Janne Elin 
Published: July 2020

ABSTRACTRotational culture promotes primary human osteoblasts (hOBs) to form three‐dimensional (3D) multicellular spheroids with bone tissue‐like structure without any scaffolding material. Cell‐based bone models enable us to investigate the effect of different agents on the mechanical strength of bone. Given that low dietary intake of both vitamin D and K is negatively associated with fracture risk, we aimed to assess the effect of these vitamins in this system. Osteospheres of hOBs were generated with menaquinone‐4 (MK‐4; 10μM) and 25‐hydroxyvitamin D3 [25(OH)D3; 0.01μM], alone and in combination, or without vitamins. The mechanical properties were tested by nanoindentation using a flat‐punch compression method, and the mineralized extracellular bone matrix was characterized by microscopy. The in vitro response of hOBs to MK‐4 and 25(OH)D3 was further evaluated in two‐dimensional (2D) cultures and in the 3D bone constructs applying gene expression analysis and multiplex immunoassays. Mechanical testing revealed that 25(OH)D3 induced a stiffer and MK‐4 a softer or more flexible osteosphere compared with control. Combined vitamin conditions induced the same flexibility as MK‐4 alone. Enhanced levels of periostin (p < 0.001) and altered distribution of collagen type I (COL‐1) were found in osteospheres supplemented with MK‐4. In contrast, 25(OH)D3 reduced COL‐1, both at the mRNA and protein levels, increased alkaline phosphatase, and stimulated mineral deposition in the osteospheres. With the two vitamins in combination, enhanced gene expression of periostin and COL‐1 was seen, as well as extended osteoid formation into the central region and increased mineral deposition all over the area. Moreover, we observed enhanced levels of osteocalcin in 2D and osteopontin in 3D cultures exposed to 25(OH)D3 alone and combined with MK‐4. In conclusion, the two vitamins seem to affect bone mechanical properties differently: vitamin D enhancing stiffness and K2 conveying flexibility to bone. These effects may translate to increased fracture resistance in vivo. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Physical Function and Health‐Related Quality of Life in Adults Treated With Asfotase Alfa for Pediatric‐Onset Hypophosphatasia
Authors: Genest Franca , Rak Dominik , Petryk Anna , Seefried Lothar 
Published: July 2020

ABSTRACTHypophosphatasia (HPP) is a rare, inherited, metabolic disease characterized by tissue‐nonspecific alkaline phosphatase deficiency resulting in musculoskeletal and systemic clinical manifestations. This observational study evaluated the effectiveness of enzyme replacement therapy with asfotase alfa on physical function and health‐related quality of life (HRQoL) among adults with pediatric‐onset HPP who received asfotase alfa for 12 months at a single center (ClinicalTrial.gov no.: NCT03418389). Primary outcomes evaluated physical function with the 6‐minute walk test (6MWT), timed up‐and‐go (TUG) test, Short Physical Performance Battery (SPPB), and handheld dynamometry (HHD). Secondary outcome measures included the Lower Extremity Functional Scale (LEFS), pain prevalence/intensity, and pain medication use; HRQoL was evaluated using the 36‐Item Short‐Form Health Survey version 2 (SF‐36v2). Safety data were collected throughout the study. All 14 patients (11 women) had compound heterozygous ALPL gene mutations and ≥1 HPP bone manifestation, including history of ≥1 fracture. Mean (min, max) age was 51 (19 to 78) years. From baseline to 12 months of treatment, median 6MWT distance increased from 267 m to 320 m (n = 13; p = 0.023); median TUG test time improved from 14.4 s to 11.3 s (n = 9; p = 0.008). Specific components of the SPPB also improved significantly: median 4‐m gait speed increased from 0.8 m/s to 1.1 m/s (n = 10; p = 0.007) and median repeated chair‐rise time improved from 22 s to 13 s (n = 9; p = 0.008). LEFS score improved from 24 points to 53 points (n = 10; p = 0.002). Improvements in HHD were not clinically significant. SF‐36v2 Physical Component Score (PCS) improved after 12 months of treatment (n = 9; p = 0.010). Pain level did not change significantly from baseline to 12 months of treatment. There were significant improvements on chair‐rise time and SF‐36v2 PCS by 3 months, and on TUG test time after 6 months. No new safety signals were identified. These results show the real‐world effectiveness of asfotase alfa in improving physical functioning and HRQoL in adults with pediatric‐onset HPP. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
β‐Elemene inhibits 7,12‐dimethylbenz(a)anthracene/12‐O‐tetradecanoylphorbol‐13‐acetate‐induced skin tumorigenesis through suppression of NF‐κB‐associated signaling events in the mouse skin model
Authors: Hu Xing , Wang Liang , Zhang Lili , Zhang Tao 
Published: July 2020

Abstractβ‐Elemene (1‐methyl‐1‐vinyl‐2,4‐diisopropenyl‐cyclohexane), a natural sesquiterpene‐derived curcumae radix, exhibits a variety of pharmacologic properties including anticancer. However, the molecular action of β‐elemene in chemical‐induced skin carcinogenesis remains unclear. Therefore, the present study executes to investigate a possible effect of β‐elemene in the 7,12‐dimethylbenz(a)anthracene (DMBA)/12‐O‐tetradecanoylphorbol‐13‐acetate (TPA)‐promoted skin tumor model. The experimental mice were subjected to execute two‐stage skin carcinogenesis and it has been initiated by the addition of DMBA on the dorsal portion of the mouse skin. One week after, for chemical carcinogen of mice, topical exposure of DMBA has been induced following with TPA (5 nmol) in acetone (200 μL) given weekly twice for 20 weeks respectively. After completion of the experimental period, we noticed that 100% of tumor incidence, histopathological changes, decreased lipid peroxidation (LPO), and decreased antioxidant levels in DMBA/TPA‐promoted skin carcinogenesis. Furthermore, enhanced activity of inflammatory protein markers (nuclear factor [NF]‐κB, tumor necrosis factor‐α, interleukin‐6, cyclooxygenase‐2, and nitric oxide synthase) and cell‐proliferative messenger RNA markers (PCNA, cyclin D1), and increased antiapoptotic protein Bcl‐2; decreased proapoptotic protein marker events Bax and caspase 3 and 9 expressions were noticed in DMBA/TPA promoted skin tissue. In this study, we noticed that β‐elemene noticeably reversed the histopathological changes and antioxidant levels in tumor‐bearing mice. Conversely, β‐elemene effectively inhibits inflammation, cell proliferation events, and enhances proapoptotic factors, by suppression of NF‐κB transcriptional activation in DMBA/TPA animals. Thus, we concluded that β‐elemene prevents DMBA/TPA promoted skin carcinogenesis through its antioxidant and abate inflammation markers and cell‐proliferative markers also activating proapoptotic molecules.
Effects of rhaponticin on retinal oxidative stress and inflammation in diabetes through NRF2/HO‐1/NF‐κB signalling
Authors: Shi Qiang , Cheng Yuhong , Dong Xiaomin , Zhang Ming , Pei Cheng , Zhang Mingzhen 
Published: July 2020

AbstractOxidative stress and inflammation have long been considered to be responsible for the development and progression of diabetic retinopathy. On the other hand, rhaponticin (RN) has received scientific attention due to its various pharmacological properties. Keeping all these in view, the present study was performed to investigate the potential protective effects of RN on the retina in diabetic rats. Rats were randomly divided into three groups: control group rats, diabetic group rats, diabetic + RN (20 mg/kg body weight for 28 days through oral route) group rats. RN supplementation to diabetic rats significantly prevent the reduction of final body weight loss, reduced weekly fasting blood glucose levels and HbA1c levels with a significant increase in serum insulin levels. quantitative polymerase chain reaction and immunohistochemical analysis found upregulation of Nrf2, NQO‐1, HO‐1 and upregulation of Keap1 genes and protein distribution along with significantly reduced levels of malondialdehyde and increased activity of superoxide dismutase, catalase and glutathione peroxidase in RN‐treated diabetic rats as compared to diabetic rats. Furthermore, treatment of diabetic rats with RN showed downregulated expression of tumour necrosis factor‐α, matrix metalloproteinase‐2 and upregulated expression of interleukin‐10 (IL‐10) and TIMP‐1 in the retina. RN treatment decreased nuclear factor kappa‐light‐chain‐enhancer of activated B cells distribution and increased IL‐10 protein distribution in the retinae of diabetic rats. In addition, RN treatment ameliorated morphological changes observed in retinae of diabetic rats. Altogether, these results provided clear evidence that treatment of diabetic rats with RN attenuated diabetic retinal changes through its hypoglycaemic, antioxidant and anti‐inflammatory effects.
COVID‐19 pandemic: Students’ perspectives on dental geriatric care and education
Authors: Brondani Mario , Donnelly Leeann 
Published: July 2020

AbstractObjectivesWith the emergence of the COVID‐19 pandemic in Canada and the curtailment of clinical and face‐to‐face university instruction in British Columbia on March 16, 2020, the opportunity arose to explore how third‐ and fourth‐year undergraduate dental students critically considered the impact of the pandemic on education and the practice of dental geriatrics.MethodsAll third‐ and fourth‐year undergraduate dental students within a dental geriatric module were asked to provide a written guided reflection on the question: “In your opinion, what factors make outbreaks (or pandemics) like COVID‐19 relevant to the practice of dental geriatrics?” Reflections were gathered from March 12 to May 8, 2020. Thematic analysis was conducted to identify and interpret patterns of meaning within the reflections by means of an interactive coding process.ResultsA total of 115 reflections, between 291 and 710 words each, were received from 56 third‐year (62.5% male) and 59 fourth‐year (42.6% male) students. Five main themes emerged: experiencing uncertainties, frailty as a moderator, constraints in accessing care, preparedness protocol, and redefining care. The frequency in which the same codes, categories, and themes were assigned varied from 16 to 140 times.ConclusionsStudents’ reflections highlighted the effects of the pandemic, not only on their education but also on frail older adults themselves and the profession of dentistry in general. Further studies are warranted to explore how this curtailment might impact educators’ approaches to geriatric education, as well as the way graduating students will set up their practices and approach geriatric care in the future.
A survey of extracorporeal photopheresis treatment in pediatric patients in the United Kingdom
Authors: Flinn Aisling M. , Macheka Sheba , Slatter Mary , Ewins Anna‐Maria , Gibson Brenda , Lawson Sarah , Tailby Anna , Lucchini Giovanna , New Helen , James Beki , Alfred Arun , Scarisbrick Julia , Gennery Andrew R 
Published: July 2020

AbstractExtracorporeal photopheresis (ECP) is a second‐line therapy in acute and chronic GVHD and solid organ transplant rejection. We report ECP use in 98 pediatric patients in seven UK centers from 2010 to 2017, the majority treated for aGVHD (73.5%). ECP was safe and well tolerated including in low body weight patients. Most patients were on multiple immunosuppressive therapies prior to ECP; 45.9% were able to reduce or stop immunosuppression with treatment. Complete or partial response was reported in almost 60%. This study supports the need to include ECP treatment data to national transplant databases to provide accurate information regarding service provision, patient outcomes, and safety.
Synthesis and evaluation of novel 1,2,4‐triazolo‐[3,4‐b]‐1,3,4‐thiadiazole tethered chalcone hybrids as potential anticancer agents
Authors: Bujji Sushmitha , Edigi Praveen Kumar , Subhashini Naikal James Prameela 
Published: July 2020

AbstractA series of novel 1,2,4‐triazolo‐[3,4‐b]‐1,3,4‐thiadiazole tethered chalcone derivatives were designed synthesized by using conventional as well as microwave assisted methods and characterized by 1H NMR, 13C NMR and mass spectral analysis. Microwave assisted synthesis caused an improvement in yield and significant reduction in the reaction time of all the derivatives. All the new synthesized derivatives were further evaluated for their anti‐cancer activity against selected four human cancer cell lines; A549 (Lung), MCF‐7 (Breast), Colo‐205 (Colon) and A2780 (Ovarian). Among the synthesized compounds, 7b, 7c, 7d, 7e, 7g and 7h exhibited potent anticancer activity compared to control drug (etoposide).
Monocytes complexed to platelets differentiate into functionally deficient dendritic cells
Authors: Singh Meera V , Suwunnakorn Sumanun , Simpson Sydney R , Weber Emily A , Singh Vir B , Kalinski Pawel , Maggirwar Sanjay B 
Published: July 2020

Abstract
In addition to their role in hemostasis, platelets store numerous immunoregulatory molecules such as CD40L, TGFβ, β2-microglobulin, and IL-1β and release them upon activation. Previous studies indicate that activated platelets form transient complexes with monocytes, especially in HIV infected individuals and induce a proinflammatory monocyte phenotype. Because monocytes can act as precursors of dendritic cells (DCs) during infection/inflammation as well as for generation of DC-based vaccine therapies, we evaluated the impact of activated platelets on monocyte differentiation into DCs. We observed that in vitro cultured DCs derived from platelet-monocyte complexes (PMCs) exhibit reduced levels of molecules critical to DC function (CD206, dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin, CD80, CD86, CCR7) and reduced antigen uptake capacity. DCs derived from PMCs also showed reduced ability to activate naïve CD4+ and CD8+ T cells, and secrete IL-12p70 in response to CD40L stimulation, resulting in decreased ability to promote type-1 immune responses to HIV antigens. Our results indicate that formation of complexes with activated platelets can suppress the development of functional DCs from such monocytes. Disruption of PMCs in vivo via antiplatelet drugs such as Clopidogrel/Prasugrel or the application of platelet-free monocytes for DCs generation in vitro, may be used to enhance immunization and augment the immune control of HIV.