bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biological role of GITR/GITRL in attributes and immune responses of macrophage
Authors: Fu Zhuo , Wang Shuang , Li Jinhua , Zhang Yunfeng , Li Han , Li Guangquan , Wan Xue , Zhang Yu 
Published: December 2019

Abstract
Glucocorticoid-induced tumor necrosis factor receptor family-related protein ligand (GITRL), a member of the tumor necrosis factor superfamily, is expressed in APCs and acts as a costimulatory molecule in the immune system. Although the glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR)/GITRL system has been modulated to promote or decrease T cell-related responses in multiple diseases, studies in macrophages are limited. To address this issue, we compared the expression of GITRL in various types of macrophages and analyzed whether GITRL can affect the fundamental properties and major functions of these cells. Our results demonstrated that M1 polarized macrophages had the highest GITRL levels. Furthermore, GITRL overexpression skewed macrophage polarization toward the M1 phenotype, accelerating proliferation and migration and regulating phagocytosis and killing function. Moreover, GITRL-silenced cells showed a loss of these functions, further confirming its vital role. We also developed an acute peritonitis mouse model, in which macrophages were driven to differentiate into a proinflammatory phenotype with GITRL up-regulation, triggering a positive feedback loop. Our results provide molecular insight into how the GITR/GITRL system modulates innate immune responses, suggesting that manipulation of the GITR/GITRL system to treat diseases depends not only on T cell regulation but also on macrophage participation.
Bispecific antibodies enhance tumor-infiltrating T cell cytotoxicity against autologous HER-2-expressing high-grade ovarian tumors
Authors: Oberg Hans-Heinrich , Janitschke Lisa , Sulaj Vjola , Weimer Jörg , Gonnermann Daniel , Hedemann Nina , Arnold Norbert , Kabelitz Dieter , Peipp Matthias , Bauerschlag Dirk , Wesch Daniela 
Published: December 2019

Abstract
Epithelial ovarian cancer displays the highest mortality of all gynecological tumors. A relapse of the disease even after successful surgical treatment is a significant problem. Resistance against the current platinum-based chemotherapeutic standard regime requires a detailed ex vivo immune profiling of tumor-infiltrating cells and the development of new therapeutic strategies.
In this study, we phenotypically and functionally characterize tumor cells and autologous tumor-derived αβ and γδ T lymphocyte subsets. Tumor-infiltrating (TIL) and tumor-ascites lymphocytes (TAL) were ex vivo isolated out of tumor tissue and ascites, respectively, from high-grade ovarian carcinoma patients (FIGO-stage IIIa-IV). We observed an increased γδ T cell percentage in ascites compared to tumor-tissue and blood of these patients, whereas CD8+ αβ T cells were increased within TAL and TIL. The number of Vδ1 and non-Vδ1/Vδ2-expressing γδ T cells was increased in the ascites and in the tumor tissue compared to the blood of the same donors. Commonly in PBL, the Vγ9 chain of the γδ T cell receptor is usually associated exclusively with the Vδ2 chain. Interestingly, we detected Vδ1 and non-Vδ1/Vδ2 T cells co-expressing Vγ9, which is so far not described for TAL and TIL.
Importantly, our data demonstrated an expression of human epidermal growth factor receptor (HER)-2 on high-grade ovarian tumors, which can serve as an efficient tumor antigen to target CD3 TIL or selectively Vγ9-expressing γδ T cells by bispecific antibodies (bsAbs) to ovarian cancer cells. Our bsAbs efficiently enhance cytotoxicity of TIL and TAL against autologous HER-2-expressing ovarian cells.
High‐dose hydroxocobalamin achieves biochemical correction and improvement of neuropsychiatric deficits in adults with late onset cobalamin C deficiency
Authors: Higashimoto Tomoyasu , Kim Alexander Y. , Ogawa Jessica T. , Sloan Jennifer L. , Almuqbil Mohammed A. , Carlson Julia M. , Manoli Irini , Venditti Charles P. , Gunay‐Aygun Meral , Wang Tao 
Published: December 2019

AbstractCobalamin C (cblC) deficiency is the most common inborn error of intracellular cobalamin metabolism caused by pathogenic variant(s) in MMACHC and manifests with methylmalonic acidemia, hyperhomocysteinemia, and hypomethioninemia with a variable age of presentation. Individuals with late‐onset cblC may be asymptomatic until manifesting neuropsychiatric symptoms, thromboembolic events, and renal disease. Although hydroxocobalamin provides a foundation for therapy, optimal dose regimen for adult patients has not been systematically evaluated. We report three adult siblings with late‐onset cblC disease, and their biochemical and clinical responses to high‐dose hydroxocobalamin. The 28‐year‐old proband presented with severe psychosis, progressive neurological deterioration, and deep venous thrombosis complicated by a pulmonary embolism. MRI studies identified lesions in the spinal cord, periventricular white matter, and basal ganglia. Serum homocysteine and methylmalonic acid levels were markedly elevated. Hydroxocobalamin at standard dose (1 mg/day) initially resulted in partial metabolic correction. A regimen of high‐dose hydroxocobalamin (25 mg/day) together with betaine and folic acid resulted in rapid and sustainable biochemical correction, resolution of psychosis, improvement of neurological functions, and amelioration of brain and spinal cord lesions. Two siblings who did not manifest neuropsychiatric symptoms or thromboembolism achieved a satisfactory metabolic control with the same high‐dose regimen. Hydroxocobalamin injection was then spaced out to 25 mg weekly with good and sustainable metabolic control. All three patients are compound heterozygotes for c.271dupA p.Arg91LysfsX14 and c.389A > G p.Tyr130Cys. This study highlights the importance of evaluating intracellular cobalamin metabolism in adults with neuropsychiatric manifestations and/or thromboembolic events, and demonstrates that high‐dose hydroxocobalamin achieves rapid and sustainable metabolic control and improvement in neuropsychiatric outcomes in adults with late‐onset cblC disease.
Treatment of dehiscence‐type defects with collagen matrix and/or enamel matrix derivative: Histomorphometric study in minipigs
Authors: França‐Grohmann Isabela Lima , Sangiorgio João Paulo Menck , Bueno Manuela Rocha , Casarin Renato Corrêa Viana , Silvério Ruiz Karina Gonzáles , Nociti Francisco Humberto , Casati Márcio Zaffalon , Sallum Enilson Antonio 
Published: December 2019

AbstractBackgroundThis study aimed to evaluate, histomorphometrically, the use of collagen matrix (CM) and/or enamel matrix derivative (EMD) for the treatment of dehiscence‐type recession defects in minipigs.MethodsEight healthy, male, young BR‐1 minipigs, with no periodontal disease were treated. Bilateral dehiscence‐type defects were surgically created on the buccal of the mandibular premolars (PI and PII). After 30 days, the defects were randomly assigned to four groups: coronally advanced flap (CAF); CAF + CM; CAF + EMD; and CAF + CM + EMD (split‐mouth design). The evaluated parameters (mm): total defect length; new cementum (NC); new bone (NB); gingival margin position; total epithelium length; epithelium on the root; connective tissue adaptation; and soft tissue thickness (STT).ResultsThe EMD‐treated groups showed a superior length of NC [4.13 ± 1.22 (CAF + EMD); 3.95 ± 1.11 (CAF + CM + EMD); 2.94 ± 0.77 (CAF + CM); 2.72 ± 0.81 (CAF), P = 0.02] and NB [3.21 ± 0.68 (CAF + CM + EMD); 3.01 ± 0.56 (CAF + EMD); 2.15 ± 0.47 (CAF + CM); 2.29 ± 0.82 (CAF), P = 0.005]. The CAF and CAF + CM groups showed a superior epithelial length when compared to EMD‐treated groups after 3 months. A superior STT was observed for CAF + CM + EMD group (1.5 ± 0.33) when compared with the other groups [1.09 ± 0.26 (CAF + EMD); 1.04 ± 0.34 (CAF + CM); and 1.14 ± 0.29 (CAF), P = 0.03].Conclusion(s)The results of the present study indicate that EMD application, irrespective of the combination with CM, may improve the periodontal regeneration of dehiscence‐type defects in this animal model.
A novel multi‐locus genetic risk score identifies patients with higher risk of generalized aggressive periodontitis
Authors: Li Wenjing , Wang Xian'e , Tian Yu , Xu Li , Zhang Li , Shi Dong , Feng Xianghui , Lu Ruifang , Meng Huanxin 
Published: December 2019

AbstractBackgroundEach genetic variant individually explains only a tiny proportion of the genetic variation with insignificant predictive power. The tool of multi‐locus genetic risk score (GRS), which aggregates information from multiple genetic variants, has been widely used in many complex diseases but not yet applied to generalized aggressive periodontitis (GAgP).MethodsA total of 335 GAgP patients and 114 healthy controls were enrolled in the case‐control study. The unweighted GRS (uGRS) and weighted GRS (wGRS) were calculated based on significant variants. Logistic regression models were conducted for the GRS‐based association analyses on the risk of GAgP. Receiver operating characteristic analysis was performed to compare the discriminatory ability of predictors of GAgP risk.ResultsFour loci were found to be significantly associated with GAgP. They were matrix metalloproteinase 8 rs11225395 (odds ratio [OR] = 1.40, 95% CI: 1.03 to 1.91), epidermal growth factor rs2237051 (OR = 1.41, 95% CI: 1.03 to 1.93), PPAR‐a rs4253623 (OR = 1.53, 95% CI: 1.03 to 2.26), and apolipoprotein E rs429358 (OR = 1.79, 95% CI: 1.08 to 2.97). Each additional point of the uGRS/wGRS was associated with a 50%/31% increased risk of developing GAgP (OR = 1.50, 95% CI: 1.21 to 1.85 or OR = 1.31, 95% CI: 1.14 to 1.51, respectively) after adjusting for age, sex, and body mass index (BMI). Participants in the high group of uGRS/wGRS (OR = 2.87, 95% CI: 1.59 to 5.17 or OR = 2.67, 95% CI: 1.46 to 4.88, respectively) and the middle group of uGRS/wGRS (OR = 2.21, 95% CI: 1.29 to 3.78 or OR = 1.88, 95% CI: 1.09 to 3.08, respectively) had an increased risk of GAgP compared with those in the low group of score after adjustment for age, sex, and BMI. The addition of GRS to a model of conventional risk factors improved discrimination by 4.5% (from 0.695 to 0.740, P = 0.048).ConclusionsWe demonstrated that the multi‐locus GRS based on four significant single nucleotide polymorphisms might be useful to assess genetic predisposition to GAgP. The GRS in combination with conventional risk factors significantly improved the power of identifying subgroups of Chinese population with a particularly high risk for GAgP.
Gun Violence Exposure and Posttraumatic Symptoms Among Children and Youth
Authors: Turner Heather A. , Mitchell Kimberly J. , Jones Lisa M. , Hamby Sherry , Wade Roy , Beseler Cheryl L. 
Published: December 2019

AbstractAlthough statistics on youth homicide and injury from gun violence are available, little research has focused on how gun violence overlaps with other victimizations or on the psychological impact of gun violence on children. Pilot survey data were collected on the experiences of 630 U.S. children (age range: 2–17 years) from Boston, Philadelphia, and rural areas of eastern Tennessee. Youth aged 10–17 years completed a self‐report survey on a wide range of gun violence exposures, and parents of younger children (aged 2–9 years) completed the survey as a proxy for that child. Direct gun violence exposure, witnessing gun violence, and hearing gunshots were all significantly associated with other forms of victimization, rs = .10–.38, p < .001. The findings suggest that youth who experience direct gun violence are often exposed to multiple violent contexts. For older youth (ages 10–17 years) polyvictimization was most strongly associated with posttraumatic symptoms, β = .35, p < .001, although witnessing gun violence still uniquely predicted a higher level of symptoms, β = .18, p < .01. For younger children (ages 2–9 years), hearing and witnessing gun violence were both related to posttraumatic symptoms, β = .15, p < .01 for both, even after controlling for polyvictimization. Mental health professionals and trauma‐informed services should be mindful that the traumatic impact of gun violence for children may not necessarily be attached to direct victimization experiences but may also result from simply seeing or hearing it in their neighborhoods.
Land cover change, landscape degradation, and restoration along a railway line in the Amazon biome, Brazil
Authors: Santos Diogo Corrêa , Souza‐Filho Pedro Walfir Martins , da Rocha Nascimento Wilson , Cardoso Gustavo Freitas , dos Santos Jorge Filipe 
Published: December 2019

AbstractRailways are known to have less influence on land use than other transportation systems. However, railways also affect biodiversity, water resources, socioeconomic outcomes, and land prices. In the context of changes in land cover and land use (LCLU) classes, this study analyses the changes arising from the establishment of the Carajás Mining Project in 1984 along the more than 900‐km length of the Carajás Railway (CRW) in southeastern Amazonia. LANDSAT‐5 (1984) and LANDSAT‐8 (2014) satellite images and human settlement layers (1990 and 2015) along CRW were used to assess LCLU changes. Satellite images were analysed with the geographic object‐based image analysis method to detect changes in LCLU classes, including municipalities located less than 50 km from the CRW. The results showed that in 1984, the areas of influence of the CRW consisted of 69% forest cover, 24% nonforest cover, 3% water, and 2% cloud cover. In 2014, forest area dropped significantly to 43%, whereas the nonforest class expanded to 46%. This analysis revealed that the conversion of forests to pastures represents the major landscape degradation that occupy 51% of the study site mainly in rural human settlement areas, which are interlinked with the construction of the CRW. Only 6% of the total area exhibits a trend of restoration marked by secondary vegetation growing. The land occupation model along the CRW is characterized by rural settlements, associated with roads and extensive pasturelands. Construction of this railway in a certain way prevented the fishbone occupation type as observed in the western Amazon.
Spatio‐temporal changes in the understory heterogeneity, diversity, and composition after fires of different severities in a semiarid oak (Quercus brantii Lindl.) forest
Authors: Heydari Mehdi , Moradizadeh Hadieh , Omidipour Reza , Mezbani Arash , Pothier David 
Published: December 2019

AbstractIn arid and semiarid forests and rangelands, native ranchers and farmers frequently use fire as a tool to improve soil fertility and vegetation composition, and to facilitate soil tilling. Investigating changes in ecosystem characteristics after these measures is of great importance for establishing management and recovery strategies. This study aimed to investigate spatial–temporal changes in the understory heterogeneity, diversity and composition after fires of different severities in a Brant's oak (Quercus brantii Lindl.) forest. Vegetation sampling was monitored in 14 patches including unburned sites (UBN), burned sites with low fire severity after 1, 5, and 10 years (LFSO, LFSF, and LFST, respectively), and burned sites with high fire severity after 1, 5, and 10 years (HFSO, HFSF, and HFST, respectively). Fire severity and time since fire significantly affected diversity indices with the lowest values of richness, evenness and diversity in high‐severity fires, while the highest values were observed in low‐severity fires. Time since fire did not significantly affect the understory evenness in both fire severities. However, species diversity and richness in low‐severity fires decreased with time since fire while the reverse was observed in high‐severity fires. The results of a detrended correspondence analysis indicated that the severity and time since fire significantly changed vegetation composition. The largest changes in vegetation composition compared to control sites were observed in HFSO, and then in HFSF and HFST. Both fire severity and time since fire caused changes in the heterogeneity of plant communities. We concluded that the use of low‐severity fires can be suitable for maintaining and increasing the heterogeneity of understory vegetation in semiarid forest ecosystems. However, low‐severity fires have also slightly, while not significantly, increased evenness and can therefore potentially reduce the ecosystem functions of dominant species in such semiarid regions. This could mitigate the positive effect of fire on vegetation heterogeneity and necessitate further investigations.
Corrosion of Mg alloys EV31A, WE43B, and ZE41A in chloride‐ and sulfate‐containing solutions saturated with magnesium hydroxide
Authors: Soltan Akif , Dargusch Matthew S. , Shi Zhiming , Gerrard Darren , Al Shabibi Sulaiman , Kuo Yu‐Chieh , Atrens Andrej 
Published: December 2019

AbstractThis study studied corrosion in 0.1 M Na2SO4, 0.1 M NaCl, and 0.6 M NaCl, all saturated with Mg(OH)2, using weight loss, hydrogen evolution, and electrochemical measurements. Corrosion was similar in all cases. Nevertheless, the corrosion rates were alloy‐dependent, were somewhat lower in 0.1 M Na2SO4 than in 0.1 M NaCl, and increased with NaCl concentration. The corrosion damage morphology was similar for all solutions; the extent correlated with the corrosion rate. The corrosion rates evaluated by the electrochemical methods were lower than those evaluated from hydrogen evolution, consistent with the Mg corrosion mechanism involving the unipositive Mg+ ion.
Targeted regions sequencing identified four novel PNPLA1 mutations in two Chinese families with autosomal recessive congenital ichthyosis
Authors: Li Liangshan , Liu Wenmiao , Xu Yinglei , Li Miaomiao , Tang Qian , Yu Bo , Cai Renmei , Liu Shiguo 
Published: December 2019

AbstractBackgroundAutosomal recessive congenital ichthyosis (ARCI) is a rare genetically heterogeneous cutaneous disease predominantly characterized by erythroderma, generalized abnormal scaling of the whole body and a collodion membrane at birth. Numerous causative genes have been demonstrated to be responsible for ARCI including PNPLA1 which can cause ARCI type 10. The objectives of this study are to describe clinical features of three ARCI patients from two Chinese unrelated families and to identify the underlying causative mutations.MethodsGenomic DNA was extracted from peripheral venous blood obtained from the two Chinese ARCI families in Shandong province. Subsequently, targeted regions sequencing (TRS) followed by Sanger sequencing was conducted to identify and validate the likely pathogenic mutations of the ARCI families.ResultsGenetic analyses revealed four novel PNPLA1 variants that are predicted to be probably to lead to ARCI in three patients of two families. Patient 1 in one family was in compound heterozygous status for c.604delC/p.Arg202Glyfs*27 and c.820dupC/p.Arg274Profs*15, whereas c.738_742delinsCCCACAGATCCTGC/ p.Gly247_Tyr248delinsProGlnIleLeuHis, and c.816dupC/p.Arg274Profs*15 were found in patient 2 and 3 of the other family. In addition, these variants cosegregate in the two pedigrees and are all within highly conserved regions of the PNPLA1 protein, which indicate that the four mutations are likely pathogenic.ConclusionOur findings not only broaden the mutational spectrum of PNPLA1, but also contribute to establishing genotype–phenotype correlations for different forms of ARCI.
Effect of Clostridium butyricum against Microglia‐Mediated Neuroinflammation in Alzheimer's Disease via Regulating Gut Microbiota and Metabolites Butyrate
Authors: Sun Jing , Xu Jingxuan , Yang Bo , Chen Keyang , Kong Yu , Fang Na , Gong Tianyu , Wang Fangyan , Ling Zongxin , Liu Jiaming 
Published: December 2019

ScopeRecent evidences demonstrate that abnormal gut microbiota (GM) might be involved in the pathogenesis of Alzheimer's disease (AD). However, the role of probiotics in preventing AD by regulating GM–gut–brain axis remains unclear. Here, the anti‐neuroinflammatory effect and its mechanism of probiotic Clostridium butyricum (CB) against AD is investigated by regulating GM–gut–brain axis.Methods and resultsAPPswe/PS1dE9 (APP/PS1) transgenic are treated intragastrically with CB for 4 weeks then cognitively tested. Amyloid‐β (Aβ) burden, microglial activation, proinflammatory cytokines production, GM, and metabolites butyrate are analyzed. Moreover, Aβ‐induced BV2 microglia are pretreated with butyrate, and the levels of cluster of differentiation 11b (CD11b), cyclooxygenase‐2 (COX‐2), and NF‐κB p65 phosphorylation are determined. The results show that CB treatment prevents cognitive impairment, Aβ deposits, microglia activation, and production of tumor necrosis factor (TNF)‐α and interleukin (IL)‐1β in the brain of APP/PS1 mice. Meanwhile, abnormal GM and butyrate are reversed after CB treatment. Notably, butyrate treatment reduces the levels of CD11b and COX‐2, and suppresses phosphorylation of NF‐κB p65 in the Aβ‐induced BV2 microglia.ConclusionsThese findings indicate that CB treatment could attenuate microglia‐mediated neuroinflammation via regulating the GM–gut–brain axis, which is mediated by the metabolite butyrate.
Ionic Liquid Based Polymer Gel Electrolytes for Use with Germanium Thin Film Anodes in Lithium Ion Batteries
Authors: McGrath Louise M. , Jones John , Carey Edwin , Rohan James F. 
Published: December 2019

AbstractThermally stable, flexible polymer gel electrolytes with high ionic conductivity are prepared by mixing the ionic liquid 1‐butyl‐1‐methylpyrrolidinium bis(trifluoromethylsulfonyl)imide (C4mpyrTFSI), LiTFSI and poly(vinylidene difluoride‐co‐hexafluoropropylene (PVDF‐HFP). FT‐IR and Raman spectroscopy show that an amorphous film is obtained for high (60 %) C4mpyrTFSI contents. Thermogravimetric analysis (TGA) confirms that the polymer gels are stable below ∼300 °C in both nitrogen and air environments. Ionic conductivity of 1.9×10−3 S cm−2 at room temperature is achieved for the 60 % ionic liquid loaded gel. Germanium (Ge) anodes maintain a coulombic efficiency above 95 % after 90 cycles in potential cycling tests with the 60 % C4mpyrTFSI polymer gel.
Qualitative and quantitative analysis of saponins in the flower bud of Panax ginseng (Ginseng Flos) by UFLC‐Triple TOF‐MS/MS and UFLC‐QTRAP‐MS/MS
Authors: Shi Jingjing , Cai Zhichen , Chen Shuyu , Zou Lisi , Liu Xunhong , Tang Renmao , Ma Jimei , Wang Chengcheng , Chen Jiali , Tan Mengxia 
Published: December 2019

AbstractIntroductionGinseng Flos (GF), the flower bud of Panax ginseng, is a worthy functional food with medicinal potential. A few studies have focused on the comprehensive and systematic analysis of its major bioactive constituents.ObjectiveThe aims are to develop the methods of ultra‐fast liquid chromatography coupled with triple quadrupole‐time of flight tandem mass spectrometry (UFLC‐Triple TOF‐MS/MS) and ultra‐fast liquid chromatography coupled with triple quadrupole‐linear ion trap tandem mass spectrometry (UFLC‐QTRAP‐MS/MS) for the qualitative and quantitative analysis of the saponins in GF.MethodologyUFLC‐Triple TOF‐MS/MS and UFLC‐QTRAP‐MS/MS were established for the qualitative and quantitative analysis of the saponins in GF, separately.ResultsFifty‐one saponins were identified in GF using UFLC‐Triple TOF‐MS/MS method; among them, 21 saponins were characterized by comparing with standards. Furthermore, 12 ginsenosides (ginsenoside Re, Rg1, Rf, 20(S)‐Rg2, 20(R)‐Rg2, Rb1, Rc, Ro, Rb2, F1, Rd, and F2) were synchronously determined by UFLC‐QTRAP‐MS/MS method after the extraction with 70% methanol. This UFLC‐QTRAP‐MS/MS method showed good linearity (r >0.9991), the interday and intraday precision, repeatability and stability were all satisfied, the average recoveries of standard addition for the compounds were between 94.01% and 105.16%, and the relative standard deviations were less than 5%.ConclusionThe results are available for the comprehensive quality control and assessment of GF and its relative products.