bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of white matter signal abnormalities on default mode network connectivity in mild cognitive impairment
Authors: Wang Zhuonan , Williams Victoria J. , Stephens Kimberly A. , Kim Chan‐Mi , Bai Lijun , Zhang Ming , Salat David H. 
Published: November 2019

AbstractRegions within the default mode network (DMN) are particularly vulnerable to Alzheimer's disease pathology and mechanisms of DMN disruption in mild cognitive impairment (MCI) are still unclear. White matter lesions are presumed to be mechanistically linked to vascular dysfunction whereas cortical atrophy may be related to neurodegeneration. We examined associations between DMN seed‐based connectivity, white matter lesion load, and cortical atrophy in MCI and cognitively healthy controls. MCI showed decreased functional connectivity (FC) between the precuneus‐seed and bilateral lateral temporal cortex (LTC), medial prefrontal cortex (mPFC), posterior cingulate cortex, and inferior parietal lobe compared to those with controls. When controlling for white matter lesion volume, DMN connectivity differences between groups were diminished within bilateral LTC, although were significantly increased in the mPFC explained by significant regional associations between white matter lesion volume and DMN connectivity only in the MCI group. When controlling for cortical thickness, DMN FC was similarly decreased across both groups. These findings suggest that white matter lesions and cortical atrophy are differentially associated with alterations in FC patterns in MCI. Associations between white matter lesions and DMN connectivity in MCI further support at least a partial but important vascular contribution to age‐associated neural and cognitive impairment.
Numerical investigation of the energy separation effect and flow mechanism inside convergent, straight, and divergent double‐sleeve RHVT
Authors: Bazgir Adib , Heydari Ali , Bazooyar Bahamin , Mohammadniakan Milad , Nabhani Nader 
Published: November 2019

AbstractThis study provides analysis of a cooled Ranque–Hilsch vortex tube (RHVT) with various specifications. It shows how cooling influences energy conversion inside the RHVT and improves performance of the device in separation of hot gas from the cold stream within the fluid by presenting the temperature detachment (the temperature diminution of cold air (ΔTc = Ti − Tc), isentropic efficiency (ηis), and coefficient of performance (COP) of divergent, convergent, and straight VTs. Two key parameters including hot tube length and number of nozzles for cooling and insulated cases are investigated to find out how the performance of the VT is affected by different geometry configurations under cooling conditions. These influences were researched for straight, convergent, and divergent VT separators under different flow characteristics. The optimum geometrical conditions for the cooling cases were identified. Results are indicative of positive influence of cooling for energy separation inside a VT. The quantities of ΔTc, ηis, and COP for the cooled RHVT are greater than uncooled RHVT for various types of VTs. Cooling the VTs leads to an increase of 12.5% in ΔTc, 14.4% in ηis, and 15.1% in COP when the base case was an uncooled VT.
Tailings from Fundão Tragedy: Physical–Chemical Properties of the Material That Remains by Candonga Dam
Authors: Figueiredo Marina Duarte , Lameiras Fernando Soares , Ardisson José Domingos , Araujo Maria Helena , Teixeira Ana Paula de Carvalho 
Published: November 2019

Abstract
In this work, samples of Fe mining tailings from the collapsed Fundão Dam, Brazil, which were retained by the Candonga hydroelectric power plant, were characterized by various techniques. Quartz, hematite, kaolinite, and goethite were identified as the main phases present. The composition, homogeneity, and relatively low (~1%) organic matter content indicate potential for usage of these tailings in civil constructions. The next step of this work is to investigate such applications. If their feasibility is confirmed, the goal is to use this material for construction in the areas affected by the Fundão Dam rupture. This use will lead to positive socio-environmental impacts in these regions, where tailings still need to be removed and damaged infrastructure needs to be repaired. Integr Environ Assess Manag 2020;16:636–642. © 2019 SETAC
PD‐1 expression affects cytokine production by ILC2 and is influenced by peroxisome proliferator‐activated receptor‐γ
Authors: Batyrova Banu , Luwaert Fien , Maravelia Panagiota , Miyabayashi Yuria , Vashist Neha , Stark Julian M. , Soori Sara Y. , Tibbitt Christopher A. , Riese Peggy , Coquet Jonathan M. , Chambers Benedict J. 
Published: November 2019

AbstractIntroductionInnate lymphoid cells (ILCs) can provide early cytokine help against a variety of pathogens in the lungs and gastrointestinal tract. Type 2 ILC (ILC2) are comparable to T helper 2 cells found in the adaptive immune system, which secrete cytokines such as interleukin 5 (IL‐5) and IL‐13 and have been found to play roles in host defense against helminth infections and in allergic responses. Recent studies have identified that programmed cell death protein 1 (PD‐1) and peroxisome proliferator activated receptor‐γ (PPAR‐γ) are highly expressed by ILC2. We examined whether PD‐1 plays a role in ILC2 function and whether there was any connection between PD‐1 and PPAR‐γMethodsTo ensure that only innate immune cells were present, ILC2 cells were examined from RAG1−/− and PD‐1−/−xRAG1−/− mice under steady‐state or following inoculation with IL‐33. We also tested ILC2 generated from bone marrow of RAG1−/− and PD‐1−/−xRAG1−/− mice for their production of cytokines. These in vitro‐derived ILC2 were also exposed to agonist and antagonist of PPAR‐γ.ResultsWe found that ILC2 from PD‐1−/−xRAG1−/− mice had reduced frequencies of IL‐5 and IL‐13 producing cells both in vitro upon IL‐33 stimulation and in vivo following intraperitoneal administration of IL‐33 when compared with ILC2 from RAG1−/− mice. However, by adding IL‐2, IL‐25, and thymic stromal lymphopoietin to the in vitro cultures, the frequency of IL‐5 and IL‐13 expressing ILC2 from PD‐1−/−xRAG1−/− mice became similar to the frequency observed for ILC2 from RAG1−/− mice. In addition, PPAR‐γ agonists and antagonists were found to increase and decrease PD‐1 expression on ILC2 respectively.ConclusionsThese findings illustrate that chronic loss of PD‐1 plays a role in ILC2 function and PD‐1 expression can be modulated by PPAR‐γ.
Insolvency law reform in Australia and Singapore: Directors' liability for insolvent trading and wrongful trading
Authors: Steele Stacey , Ramsay Ian , Webster Miranda 
Published: November 2019

AbstractThis article compares reforms to directors' liability for insolvent trading in Singapore and in Australia. We analyse the law in these two countries because they are important Asia‐Pacific trading partners and their laws were originally largely the same—Singapore's law on insolvent trading reflected the law in Australia from the 1960s. However, the law in the two countries has now diverged substantially. The comparison of these two countries therefore represents an interesting case study in how countries differ in their approaches to balancing the competing interests evident in laws that impose personal liability on company directors for insolvent trading. Reform of the prohibition against insolvent trading was a focus of Australia's insolvency law reforms in 2017, which led to the introduction of a safe harbour for directors from liability. Singapore's omnibus insolvency law reforms of 2018–19 include amendments to update Singapore's fraudulent and insolvent trading provisions by introducing a concept of “wrongful trading.” The article finds that there are some areas of convergence between these two jurisdictions when it comes to debates about such provisions but concludes that the different contemporary legislative histories in Australia and Singapore have affected their approaches to reform. Reformers in both jurisdictions have attempted to find an appropriate balance between protecting creditors, discouraging director misconduct, and encouraging entrepreneurship and innovation; however, this comparison suggests that the weight that reformers place on creditor protection compared with the concern that excessive personal liability can make directors unduly risk‐averse is influenced by their existing legislative framework and experience of those laws. Although Australia has shifted away from a strict focus on creditor protection, to give directors more opportunities to engage in restructuring, Singapore's amendments may provide a more creditor‐friendly regime.
Placental fibronectin staining is unaffected in pregnancies complicated by late‐onset intrauterine growth restriction and small for gestational age fetuses
Authors: Fruscalzo Arrigo , Londero Ambrogio P. , Orsaria Maria , Marzinotto Stefania , Driul Lorenza , Di Loreto Carla , Mariuzzi Laura 
Published: November 2019

AbstractObjectiveTo investigate the placental staining pattern of fibronectin, an extracellular matrix protein essential for trophoblastic invasion, in pre‐eclampsia and fetal growth restriction.MethodsThis was a retrospective study conducted at the University of Udine, including the placentas of women with pre‐eclampsia and fetal growth restriction collected between January 1, 2001, and December 31, 2010. Fibronectin was evaluated in placental tissue micro‐array by immunohistochemistry, describing localization and intensity of staining.ResultsThe study included the placentas of 36 women with early‐onset (delivery <34 weeks of gestation) pre‐eclampsia; 6 with early‐onset HELLP syndrome; 17 with early‐onset intrauterine growth restriction (IUGR); 14 with late‐onset (delivery ≥34 weeks of gestation) pre‐eclampsia; 35 with late‐onset IUGR; 18 with small for gestational age (SGA) fetuses (birth weight <10th percentile); and 64 controls. Fibronectin was present both at the cell surface and in the cytoplasm. Cytoplasm staining intensity resulted higher in early forms of pregnancy‐related complications compared to controls, although this was statistically significant (P<0.05) only for early‐onset pre‐eclampsia (P=0.085 for HELLP syndrome; P=0.091 for IUGR). Also, late‐onset forms of pre‐eclampsia had stronger cytoplasmic and pericellular staining compared to controls (P<0.05). Interestingly, staining of both late‐onset IUGR and SGA was comparable to controls.ConclusionFibronectin appeared to be unaffected in women with late‐onset IUGR and SGA fetuses, suggesting a peculiar common pathogenetic pattern in these conditions.
The combination of two‐dimensional and three‐dimensional analysis methods contributes to the understanding of glioblastoma spatial heterogeneity
Authors: Yang Runwei , Guo Jinglin , Lin Zhiying , Song Haimin , Feng Zhanpeng , Ou Yichao , Zhou Mingfeng , Li Yaomin , Yi Guozhong , Li Ke , Li Kaishu , Guo Manlan , Wang Xiran , Huang Guanglong , Liu Zhifeng , Qi Songtao , Liu Yawei 
Published: November 2019

AbstractHeterogeneity is regarded as the major factor leading to the poor outcomes of glioblastoma (GBM) patients. However, conventional two‐dimensional (2D) analysis methods, such as immunohistochemistry and immunofluorescence, have limited capacity to reveal GBM spatial heterogeneity. Thus, we sought to develop an effective analysis strategy to increase the understanding of GBM spatial heterogeneity. Here, 2D and three‐dimensional (3D) analysis methods were compared for the examination of cell morphology, cell distribution and large intact structures, and both types of methods were employed to dissect GBM spatial heterogeneity. The results showed that 2D assays showed only cross‐sections of specimens but provided a full view. To visualize intact GBM specimens in 3D without sectioning, the optical tissue clearing methods CUBIC and iDISCO+ were used to clear opaque specimens so that they would become more transparent, after which the specimens were imaged with a two‐photon microscope. The 3D analysis methods showed specimens at a large spatial scale at cell‐level resolution and had overwhelming advantages in comparison to the 2D methods. Furthermore, in 3D, heterogeneity in terms of cell stemness, the microvasculature, and immune cell infiltration within GBM was comprehensively observed and analysed. Overall, we propose that 2D and 3D analysis methods should be combined to provide much greater detail to increase the understanding of GBM spatial heterogeneity.
Anti‐inflammatory effects of doxepin hydrochloride against LPS‐induced C6‐glioma cell inflammatory reaction by PI3K‐mediated Akt signaling
Authors: Tao Feng , Zhu Jie , Duan Lijie , Wu Junfeng , Zhang Jianfeng , Yao Kai , Bo Jimei , Zu Hengbing 
Published: November 2019

AbstractRecent studies have shown that tricyclic antidepressants (TCAs) may have anti‐inflammatory and anticonvulsant effects in addition to its antidepressant effects. So far, the nonantidepressant effects of TCAs and their molecular pharmacological mechanisms remain completely unclear. Chronic inflammation in the brain parenchyma may be related to the pathogenesis and progression of various neurodegenerative diseases. As a common antidepressant and anti‐insomnia drug, doxepin also may be a potential anti‐inflammatory and anticonvulsant drug, so the study on the anti‐inflammatory protective effect of doxepin and its molecular mechanism has become a very important issue in pharmacology and clinical medicine. Further elucidating the anti‐inflammatory and neuroprotective effects of doxepin and its molecular mechanism may provide the important theoretical and clinical basis for the prevention and treatment of neurodegenerative disease. This study was designed to understand the glio‐protective mechanism of doxepin against the inflammatory damage induced by lipopolysaccharide (LPS) exposure in C6‐glioma cells. We found the treatment of C6‐glioma cells with LPS results in deleterious effects, including the augmentation of inflammatory cytokine levels (tumor necrosis factor‐α, interleukin‐1β), and suppresses the Akt phosphorylation. Furthermore, our outcomes demonstrated that doxepin was able to suppress these effects induced by LPS, through activation of the phosphatidylinositol‐3‐kinase‐mediated protein kinase B (Akt) pathway. To sum up, these results highlight the potential role of doxepin against neuroinflammatory‐related disease in the brain.
Mg2+ in β‐TCP/Mg–Zn composite enhances the differentiation of human bone marrow stromal cells into osteoblasts through MAPK‐regulated Runx2/Osx
Authors: Wang Zhenting , Liu Qing , Liu Congcong , Tan Wei , Tang Mingying , Zhou Xiaohua , Sun Tianshi , Deng Youwen 
Published: November 2019

AbstractInducing the osteogenic differentiation from bone marrow stromal cells (BMSCs) might be a potent strategy for treating bone loss and nonunion during fracture and improving fracture healing. Among several signaling pathways involved, mitogen‐activated protein kinases (MAPKs) have been reported to play a critical role. Magnesium (Mg)‐based alloys, including Mg–Zn alloy, have been used clinically as implants in the musculoskeletal field and could promote BMSC osteogenic differentiation. However, the underlying mechanisms remain unclear. In this study, we produced Mg–Zn alloy consists of Mg and low concentrations of Zn, calcium carbonate, and β‐tricalcium phosphate (β‐TCP; manifesting process not shown), prepared Mg, Zn, and Mg–Zn extracts, and investigated the specific effects of these extracts on human BMSC (hBMSC) osteogenic differentiation and MAPK signaling. Mg extracts and Mg–Zn extracts could significantly promote the osteogenic differentiation of hBMSCs as manifested as increased alkaline phosphatase levels, enhanced calcium nodules formation, and increased messenger RNA expression and protein levels of osteogenesis markers, including BMPs, Col‐I, Runx2, and Osx; in the meantime, Mg culture medium (CM) and Mg–Zn CM both significantly enhanced the activation of MAPK signaling in hBMSCs. By adding ERK1/2 signaling, p38 signaling, or JNK signaling inhibitor to Mg–Zn CM, or conducting p38 MAPK silence in hBMSCs, we revealed that these extracts might promote hBMSC osteogenic differentiation via p38 MAPK signaling and MAPK‐regulated Runx2/Osx. In conclusion, Mg2+ in β‐TCP/Mg–Zn extract promotes the osteogenic differentiation of hBMSCs via MAPK‐regulated Runx2/Osx interaction.
John Tyler Bonner: Remembering a scientific pioneer
Authors: Brigandt Ingo , Katz Laura A. , Nanjundiah Vidyanand , Gilbert Scott F. , Grant Peter R. , Grant B. Rosemary , Love Alan C. , Newman Stuart A. , West‐Eberhard Mary J. 
Published: November 2019

AbstractThroughout his life, John Tyler Bonner contributed to major transformations in the fields of developmental and evolutionary biology. He pondered the evolution of complexity and the significance of randomness in evolution, and was instrumental in the formation of evolutionary developmental biology. His contributions were vast, ranging from highly technical scientific articles to numerous books written for a broad audience. This historical vignette gathers reflections by several prominent researchers on the greatness of John Bonner and the implications of his work
Liver gene transfection by retrograde intrabiliary infusion facilitated by temporary biliary obstruction
Authors: Dai Chenguang , Wang Min , Zhao Lili , Xu Chunfang , Huang Jin , Fan Zhining 
Published: November 2019

AbstractBackgroundThe hepatobiliary tract may be a valuable administration site for gene delivery. We demonstrated the role of temporary biliary obstruction for gene transfection by retrograde intrabiliary infusion.MethodsMale Sprague–Dawley rats received intrabiliary infusion of luciferase plasmid via an artificial common bile duct, with temporary biliary obstruction for 0 minutes (NO group), 30 minutes (30 min group) and 24 hours (24 h group), respectively (n = 4 for each group). Gene expression levels were evaluated by luciferase bioluminescence on postoperative days (POD) 1, 2 and 7. Serum and livers were collected on POD 1 and 14 for liver biochemistry, hematoxylin and eosin staining, and immunohistochemistry.ResultsOn POD 1, luciferase chemoluminescence was significantly higher in the 24 h group than in the NO group (p = 0.002) and the 30 min group (p = 0.002). However, it decreased rapidly after reversal of the obstruction in the 24 h group (POD 1 versus POD 2, p = 0.002; POD 1 versus POD 7, p = 0.002). Liver biochemistry was changed on POD 1, but no significant differences were detected after 14 days of recovery (p > 0.05). Similar histological changes were found in the three groups, with no unwanted proliferation of biliary epithelial cells. The obstruction did not cause serious liver damage.ConclusionsTemporary biliary obstruction for 24 hours facilitated the safe, feasible and effective transfection of plasmid DNA into the liver via the hepatobiliary tract. In the future, endoscopic retrograde cholangiopancreatography and its dilation balloon could be used to create biliary obstruction and allow the direct gene delivery into the liver. More research is necessary for achieving stable gene expression, as well as in terms of weighing its benefits against potential complications.
Carl Gustav Jung and Albert Einstein: An ambivalent relationship
Authors: Lukács Orsolya 
Published: November 2019

AbstractDespite Carl Gustav Jung's acknowledgment of Albert Einstein's influence on his thinking, and despite the significant number of studies about Jung's interest in physics—and his collaboration with the theoretical physicist Wolfgang Pauli—so far there has been no thorough investigation into the connection between Jung and Einstein. This paper fills the void by reconstructing the circumstances of the meetings between the two men; by analysing the dynamics and importance of their relationship and by offering insights into the reasons why the connection did not last. The reconstruction of the narrative of this connection serves as a good foundation for future research into Einstein's intellectual influence on Jung.
Catalyst‐free straightforward synthesis of 3‐cyano‐3‐arylamino‐2‐oxindoles through hydrocyanation with benzoyl cyanide
Authors: Chen Xiao , Li Zheng 
Published: November 2019

AbstractThe effective hydrocyanation of 3‐(arylimino)indolin‐2‐ones with benzoyl cyanide under catalyst‐free condition at room temperature to synthesize 3‐cyano‐3‐arylamino‐2‐oxindoles is described. This protocol benefits from low toxicity, inexpensive, and easy‐to‐handle cyanating agent, no catalysts, no additives, mild conditions, good substrate tolerance, and simple work‐up procedure. This reaction successfully offers an alternative to structurally diverse 3,3‐disubstituted oxindoles.
Comparison of cumulative viraemia following treatment initiation with different antiretroviral regimens: a real‐life study in Brazil
Authors: Pascom Ana R , Pinho Rosana EGG , Rick Fernanda , Veras Nazle MC , Perini Filipe de Barros , Meireles Mariana V , Pereira Gerson F , Benzaken Adele S , Avelino‐Silva Vivian I 
Published: November 2019

AbstractIntroductionThe relative efficacy of different antiretroviral (ART) regimens has been extensively evaluated in the context of clinical trials, using HIV viral load (VL) measurements at pre‐specified timepoints after ART onset. However, data from real‐life studies using combined longitudinal measurements of cumulative viraemia are scarce. This study aimed to address the independent effect of different ART regimens on HIV cumulative viraemia over the first 12 months after treatment initiation, using programmatic data from the Ministry of Health of Brazil.MethodsRetrospective cohort study analysing cumulative viraemia under the most frequently used ART regimens in Brazil (tenofovir, lamivudine and dolutegravir (regimen 1); tenofovir, lamivudine and efavirenz (regimen 2); tenofovir, lamivudine and ritonavir‐boosted atazanavir (regimen 3)).Results and DiscussionWe included 112,243 patients >12 years old who received their first ART prescription between January 2014 and August 2017. Univariate analysis indicated that cumulative viraemia was significantly lower in patients receiving regimen 1 as compared with those receiving regimens 2 or 3 (p<0.0001 for both pairwise comparisons). In a multivariable analysis adjusted for age, sex, baseline T CD4+ counts and baseline HIV VL, ART regimen persisted with statistically significant effect on 12‐month cumulative viraemia. The model predicted a 45‐unit increase in log10 copy‐days/mL cumulative viraemia for regimen 2 as compared with regimen 1, and a 70‐unit increase in log10 copy‐days/mL cumulative viraemia for regimen 3 as compared with regimen 1 (95%CI 41 to 49 and 61 to 79 respectively; p<0.001 for both comparisons). In models restricted to youths (13 to 24 years old) and female patients, ART regimen had similar effects. ART regimen with dolutegravir in association with a tenofovir‐lamivudine backbone was superior to regimens containing efavirenz or boosted atazanavir in reducing HIV VL, as shown by cumulative viraemia over the first 12 months after treatment initiation. The superiority persisted even after adjusting the analysis for potential confounders.ConclusionsOur findings could bring direct benefits to patients as suggested by lower viral replication during treatment, lower risk of HIV transmission, and a potential reduction in resistance mutations in the initial 12 months under ART.