bluuebunny/crossref_metadata_2025 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

Regions 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

This 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

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

Introduction

Innate 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‐γ

Methods

To 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.

Results

We 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.

Conclusions

These 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

This 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

Objective

To investigate the placental staining pattern of fibronectin, an extracellular matrix protein essential for trophoblastic invasion, in pre‐eclampsia and fetal growth restriction.

Methods

This 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.

Results

The 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.

Conclusion

Fibronectin 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

Heterogeneity 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

Recent 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

Inducing 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

Throughout 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

Background

The 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.

Methods

Male 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.

Results

On 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.

Conclusions

Temporary 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

Despite 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

The 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

Introduction

The 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.

Methods

Retrospective 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 Discussion

We 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.

Conclusions

Our 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.
Good to be bad: Should we be worried by the sharing economy?
Authors: Chalmers Dominic , Matthews Russell
Published: November 2019

We develop the notion of a legitimacy tipping point to demonstrate how informal economy practices are being utilized by innovative sharing economy ventures to gain a competitive advantage that is subsequently leveraged to reconfigure formal institutional arrangements. Companies who are able to scale rapidly can afford to contravene regulations, provided they have public support. When they reach a certain size, in terms of investment and customer numbers, regulators are forced into a reactive position where novel business models are legitimized. This raises an important question for regulators and entrepreneurs as to whether subverting business regulation is being viewed as a viable source of competitive advantage by scaling firms.
Conceptualizing and measuring strategy implementation: A multidimensional view
Authors: Amoo Nii , Hiddlestone‐Mumford Jacqueline , Ruzibuka John , Akwei Cynthia
Published: November 2019

When it comes to strategy making and strategy implementation, although it is acknowledged that the biggest challenge is the implementation, most of the literature tends to focus more on the strategy making part. Just like how the strategy implementation part of the strategy process has received little attention in the strategic planning literature, equally there are not much research devoted to developing measures for studying this important management process and practice. Through quantitative methodological approaches for studying the strategic management and planning process, and analysis of data from 208 senior managers involved in strategy processes within ten UK industrial sectors, this paper addresses this void by presenting evidence on the measurement properties of a multi‐dimensional instrument that assesses ten dimensions of strategy implementation. Using exploratory factor analysis, results indicate the sub‐constructs (the ten dimensions) are uni‐dimensional factors with acceptable reliability and validity. Furthermore, using three additional measures, a correlation and hierarchical regression analysis,the nomological validity for the multi‐dimensional strategy implementation construct was also established. Relative importance of ten strategy implementation dimensions (activities) for practising managers is highlighted, with the mutually and combinative effects and drawing conclusion that senior management involvement leads the way among the ten key identified activities vital for successful strategy implementation.
Strategic management: The evolution of the field
Authors: Bindra Sunali , Parameswar Nakul , Dhir Sanjay
Published: November 2019

The merger of “plan” and “pattern” sects of research is essential for the understanding of strategic management understanding and will pose significant methodological challenges. Detailed firm‐ and industry‐level data over long periods will unravel path dependencies. The underlying strategy variables used are causally ambiguous and difficult to measure.
Stakeholder salience and collaboration decisions in microfinance organizations: Evidence from developing Islamic country's context
Authors: Khurram Shahzad , Khurram Anjeela , Memon Mumtaz Ali
Published: November 2019

Studies mutually disagree on which stakeholders matter to the managers. Based on a finer differentiation of salience attributes—power, legitimacy, urgency, and proximity—this study finds that stakeholders that possess four attributes' types—that is, structural legitimacy, utilitarian power, organized proximity, and criticality—are considered salient by managers of microfinance organizations. Collaboration with salient stakeholders is considered indispensable by microfinance managers.
Extra‐articular resection for bone sarcomas involving the hip joint
Authors: Fujiwara Tomohiro , Tsuda Yusuke , Evans Scott , Stevenson Jonathan , Parry Michael , Jeys Lee , Abudu Adesegun
Published: November 2019

Aim

The aim of this study was to determine the oncologic, functional, and clinical outcomes after the extra‐articular resection and limb‐salvage reconstruction of the hip joint.

Methods

A retrospective study of 34 patients who underwent extra‐articular resection of the hip joint for bone sarcomas between 1996 and 2016 was conducted. The primary tumor site was pelvis in 26 patients (76%) and femur in eight (24%).

Results

The surgical margins achieved were clear in 31 (91%) patients, and seven (21%) patients developed local recurrence; mostly occurring in pelvic tumors (n = 6). The 3‐year overall survival was 63% with a median follow‐up of 38 months (range, 5‐219), which showed no statistical difference in tumor location. The most common complication was deep infection (n = 7) and dislocation (n = 7), mostly seen in pelvic tumors. Implant failure was seen in two patients with pelvic tumors, while no failure was noted in patients with femoral tumors. The median Musculoskeletal Tumour Society score was 69%; 67% for pelvic tumors and 73% for femoral tumors (P = .535).

Conclusion

Despite complex surgery, extra‐articular resection of the hip joint can achieve oncologically and functionally acceptable outcomes. While tumors of the pelvis are associated with a higher incidence of infection and local recurrence after resection, resection of tumors involving the femur are well tolerated.
Think global, act local: The small‐scale environment mainly influences microbial community development and function in lake sediment
Authors: Orland Chloé , Yakimovich Kurt M. , Mykytczuk Nadia C. S. , Basiliko Nathan , Tanentzap Andrew J.
Published: November 2019

The early stages of community development influence longer‐term establishment of species, traits, and ultimately ecosystem function. How this process varies with small‐ and large‐scale abiotic and biotic conditions is poorly studied in microbes. Here, we tested how different spatial scales influenced the rate at which taxonomic and functional composition of microbial communities changed over time in lake sediments, and whether these changes occurred synchronously across different environments given the same initial communities. We manipulated the small‐scale environment by creating sediments with different terrestrial organic matter (t‐OM) quantity and quality, and placing these in two lakes differing in trophic status to vary the large‐scale environment. We found that archaeal and bacterial communities, but not fungi, became taxonomically dissimilar over 2 months despite being derived from the same initial leaf material, primarily because of small‐scale environmental conditions. Sediment t‐OM quantity consistently explained changes in community composition both temporally within mesocosms and spatially between mesocosms in different lakes. Archaea, bacteria, and fungi also varied by up to 10 times in how quickly they changed, providing among the first evidence in the same study system that they respond differently over time to abiotic and biotic conditions. Finally, functional composition was influenced by both small‐ and large‐scale environmental conditions, with genes involved in t‐OM decomposition showing some of the largest changes in abundance after 1 yr. Our study highlights that future changes to both sediments and lake waters can modify how sediment microbial communities develop with consequences for important ecosystem functions like carbon cycling.
Comparative genomics of hepatitis A virus, hepatitis C virus, and hepatitis E virus provides insights into the evolutionary history of Hepatovirus species
Authors: Wassenaar Trudy M. , Jun Se‐Ran , Robeson Michael , Ussery David W.
Published: November 2019

The intraspecies genomic diversity of the single‐strand RNA (+) virus species hepatitis A virus (Hepatovirus), hepatitis C virus (Hepacivirus), and hepatitis E virus (Orthohepevirus) was compared. These viral species all can cause liver inflammation (hepatitis), but share no gene similarity. The codon usage of human hepatitis A virus (HAV) is suboptimal for replication in its host, a characteristic it shares with taxonomically related rodent, simian, and bat hepatitis A virus species. We found this codon usage to be strikingly similar to that of Triatoma virus that infects blood‐sucking kissing bugs. The codon usage of that virus is well adapted to its insect host. The codon usage of HAV is also similar to other invertebrate viruses of various taxonomic families. An evolutionary ancestor of HAV and related virus species is hypothesized to be an insect virus that underwent a host jump to infect mammals. The similarity between HAV and invertebrate viruses goes beyond codon usage, as they also share amino acid composition characteristics, while not sharing direct sequence homology. In contrast, hepatitis C virus and hepatitis E virus are highly similar in codon usage preference, nucleotide composition, and amino acid composition, and share these characteristics with Human pegivirus A, West Nile virus, and Zika virus. We present evidence that these observations are only partly explained by differences in nucleotide composition of the complete viral codon regions. We consider the combination of nucleotide composition, amino acid composition, and codon usage preference suitable to provide information on possible evolutionary similarities between distant virus species that cannot be investigated by phylogeny.
Hyperphosphorylated Tau, Increased Adenylate Cyclase 5 (ADCY5) Immunoreactivity, but No Neuronal Loss in ADCY5‐Dyskinesia
Authors: Chen Dong‐Hui , Latimer Caitlin S. , Spencer Min , Karna Prasanthi , Gonzalez‐Cuyar Luis F. , Davis Marie Y. , Keene C. Dirk , Bird Thomas D. , Raskind Wendy H.
Published: November 2019

Background

Adenylate cyclase 5 (ADCY5)‐related dyskinesia is a childhood‐onset movement disorder. Manifestations vary in frequency and severity and may include chorea, tremor, dystonia, facial twitches, myoclonus, axial hypotonia, and limb hypertonia. Psychosis is likely part of the broader spectrum. ADCY5 is widely expressed in the brain, especially in the striatum. Previous reports of brain autopsies of 2 subjects with likely ADCY5‐dyskinesia were limited by the absence of a molecular diagnosis. In 1 case, normal gross pathology was reported. In the other case, ADCY5 expression was not examined and neuropathological findings were confounded by age and comorbidities.

Objectives

To examine ADCY5 expression and neuropathological changes in ADCY5‐dyskinesia.

Methods

An extensive brain autopsy, including immunohistochemical analyses with antibodies to paired helical filament tau, α‐synuclein, amyloid‐β, microtubule‐associated protein 2, and ADCY5, was performed.

Results

The patient, with a p.M1029K ADCY5 variant, had severe dyskinesias from early childhood, later recurrent episodes of psychosis, and died at age 46. Gross pathology was unremarkable, but we detected increased immunoreactivity for ADCY5 in neurons in multiple brain regions. Despite no history of brain trauma to suggest chronic traumatic encephalopathy, we found tau deposits in the deep cortical sulci, midbrain, and hippocampus with minimal amyloid pathology and no Lewy bodies.

Conclusions

We present the first brain autopsy findings in a molecularly proven case of ADCY5‐dyskinesia, showing increased ADCY5 immunoreactivity in neurons and evidence of tau deposition. Additional patients will need to be studied to determine whether increased immunoreactivity for ADCY5 is a signature for ADCY5‐dyskinesia and whether this disease has a tauopathy component.
A measure of authorship by publications
Authors: Mukherjee Conan , Basu Ranojoy , Alam Aftab
Published: November 2019

Measuring publication success of a researcher is a complicated task as publications are often co‐authored by multiple authors, and so, it requires comparison of solo publications with joint publications. In this paper, like Price (1981), we argue for an egalitarian perspective in accomplishing this task.

More specifically, we justify the need for an ethical perspective in quantifying academic author by identifying certain ethical difficulties of some popular contemporary indices used for this purpose. And then we show that for any given dataset of research papers, the unique method satisfying the ethical notions of identity independence and performance invariance must be the egaliatarian E‐index proposed by Bose, Pal, and Sappington (2010) and Price (1981). In our setting, this egalitarian method divides authorship of joint projects equally among authors and sums across all publications of each author.
Therapy‐refractory schizophrenia in a patient who previously suffered from Meige’s syndrome
Authors: Uemura Tomihiko , Mochida Masahiko , Matsumi Tatsunaru , Yoshimoto Katsuhiko , Tatebayashi Yoshitaka
Published: November 2019

The main symptoms of Meige's syndrome are involuntary eye blinking with muddled speech and uncontrollable contraction of the platysma muscle characterized by segmental, primarily oromandibular, dystonia (hyperkinesia). It can also develop after long‐term medication of first‐ and second‐generation antipsychotics. Here, we report the case of a Japanese female schizophrenic patient comorbid with Meige's syndrome and hyperthyroidism. We discuss the relationship between the three diseases, that is, schizophrenia, Meige's syndrome, and hyperthyroidism. Our intention is to consider the important role of the cerebral basal ganglia, where little attention has been given in regard to schizophrenia and Meige's syndrome. A part of this article was presented in a poster section at the joint congress of the 28th Annual Meeting of the Japanese Society of Clinical Neuropsychopharmacology and the 48th Annual Meeting of the Japanese Society of Neuropsychopharmacology held in 2018.
Conversion of cationic amphiphilic lytic peptides to cell‐penetration peptides
Authors: Yu Hao‐Hsin , Sakamoto Kentarou , Akishiba Misao , Tamemoto Naoki , Hirose Hisaaki , Nakase Ikuhiko , Imanishi Miki , Madani Fatemeh , Gräslund Astrid , Futaki Shiroh
Published: November 2019

Accomplishment of efficient intracellular delivery of bioactive peptides and proteins have been reported via conjugation of peptides having membrane permeation ability (i.e., cell‐penetrating peptides [CPPs]), where a physiological uptake system of extracellular materials, endocytosis, often plays a role. When endocytosed, the bioactive peptides and proteins are encapsulated into vesicular compartment named endosomes, and have to escape into the cytosol with the help of tethered CPPs for obtaining the expected bioactivities. Therefore, CPPs having improved endosomolytic activity is necessary. We here introduce an approach to employ hemolytic peptides as a new class of CPPs, which was designed to attenuate their membrane perturbation ability on cell surfaces while recovering the membrane lytic activity under endosomal conditions (i.e., the attenuated cationic amphiphilic lytic [ACAL] peptides). This was realized by introducing negatively charged glutamic acid (Glu) residues into the potential hydrophobic face of the cationic amphiphilic peptides. The applicability of these peptides for CPPs was evaluated through the intracellular delivery of shepherdin, an apoptosis‐inducing peptide.
Altered Pharmacokinetics and Dosing of Liposomal Amphotericin B and Isavuconazole during Extracorporeal Membrane Oxygenation
Authors: Zhao Yanjun , Seelhammer Troy G. , Barreto Erin F. , Wilson John W.
Published: November 2019

Drug pharmacokinetics may be significantly altered in patients receiving extracorporeal membrane oxygenation (ECMO). Ensuring the optimized effective dosing of antimicrobials on ECMO remains a challenge. To date, limited data are available regarding the optimal use of amphotericin and triazoles during ECMO. We report a case of altered pharmacokinetics, insufficient liposomal amphotericin B and isavuconazole levels, and the need for escalated doses during ECMO in a patient with severe acute respiratory distress syndrome secondary to pulmonary blastomycosis. A 2‐fold increase in the standard total daily dose of both drugs was necessary to overcome low serum concentrations thought to be secondary to drug loss from ECMO circuit sequestration. These findings have important implications for optimizing antimicrobial therapy in patients receiving ECMO to maximize therapeutic efficacy. The use of therapeutic drug monitoring for patients receiving antimicrobial therapy with concurrent ECMO may facilitate appropriate drug dosing to achieve adequate serum concentrations and optimize favorable patient outcomes. Further studies exploring antimicrobial pharmacokinetics during ECMO are needed to inform dosing recommendations in critically ill patients.
PSMA ADC monotherapy in patients with progressive metastatic castration‐resistant prostate cancer following abiraterone and/or enzalutamide: Efficacy and safety in open‐label single‐arm phase 2 study
Authors: Petrylak Daniel P. , Vogelzang Nicholas J. , Chatta Kamal , Fleming Mark T. , Smith David C. , Appleman Leonard J. , Hussain Arif , Modiano Manuel , Singh Parminder , Tagawa Scott T. , Gore Ira , McClay Edward F. , Mega Anthony E. , Sartor A. Oliver , Somer Bradley , Wadlow Raymond , Shore Neal D. , Olson William C. , Stambler Nancy , DiPippo Vincent A. , Israel Robert J.
Published: November 2019

Background

Prostate‐specific membrane antigen (PSMA) is a well‐established therapeutic and diagnostic target overexpressed in both primary and metastatic prostate cancers. PSMA antibody‐drug conjugate (PSMA ADC) is a fully human immunoglobulin G1 anti‐PSMA monoclonal antibody conjugated to monomethylauristatin E, which binds to PSMA‐positive cells and induces cytotoxicity. In a phase 1 study, PSMA ADC was well tolerated and demonstrated activity as measured by reductions in serum prostate‐specific antigen (PSA) and circulating tumor cells (CTCs). To further assess PSMA ADC, we conducted a phase 2 trial in metastatic castration‐resistant prostate cancer (mCRPC) subjects who progressed following abiraterone/enzalutamide (abi/enz) therapy.

Methods

A total of 119 (84 chemotherapy‐experienced and 35 chemotherapy‐naïve) subjects were administered PSMA ADC 2.5 or 2.3 mg/kg IV q3w for up to eight cycles. Antitumor activity (best percentage declines in PSA and CTCs from baseline and tumor responses through radiological imaging), exploratory biomarkers, and safety (monitoring of adverse events [AEs], clinical laboratory tests, and Eastern Cooperative Oncology Group performance status) were assessed.

Results

PSA declines ≥50% occurred in 14% of all treated (n = 113) and 21% of chemotherapy‐naïve subjects (n = 34). CTC declines ≥50% were seen in 78% of all treated (n = 77; number of subjects with ≥5 CTCs at baseline and a posttreatment result) and 89% of chemotherapy‐naïve subjects (n = 19); 47% of all treated and 53% of chemotherapy‐naïve subjects had a transition from ≥5 to less than 5 CTCs/7.5 mL blood at some point during the study. PSA and CTC reductions were associated with high PSMA expression (CTCs or tumor tissue) and low neuroendocrine serum markers. In the chemotherapy‐experienced group, the best overall radiologic response to PSMA ADC treatment was stable disease in 51 (60.7%) subjects; 5.7% of subjects in the chemotherapy‐naïve group had partial responses. The most common treatment‐related AEs ≥Common Terminology Criteria for AE (CTCAE) grade 3 were neutropenia, fatigue, electrolyte imbalance, anemia, and neuropathy. The most common serious AEs were dehydration, hyponatremia, febrile neutropenia, and constipation. Two subjects who received 2.5 mg/kg died of sepsis.

Conclusions

PSMA ADC demonstrated some activity with respect to PSA declines, CTC conversions/reductions, and radiologic assessments in abi/enz treated mCRPC subjects. Clinically significant treatment‐related AEs included neutropenia and neuropathy.
A progressive mean control chart for monitoring time between events
Authors: Alevizakos Vasileios , Koukouvinos Christos
Published: November 2019

Control charts based on time between events (TBE) are widely used in high‐quality manufacturing processes where the events occur rarely. For monitoring such data, a new two‐sided TBE control chart called progressive mean control chart (regarded as PM‐TBE chart) is proposed in the present study. Through a simulation study and using the average run‐length (ARL) measure, it is shown that the proposed chart outperforms the tr, ARL‐unbiased gamma, GWMA‐TBE, and DEWMA‐TBE charts in detecting very small to moderate downward shifts, as well as in some cases small upward shifts. Moreover, the PM‐TBE chart is very robust for moderate to large shifts when the true distribution of the TBE observations is a Weibull or a lognormal. Finally, examples are given to display the application of the proposed chart.
Dynamical Signatures of Ground‐State Degeneracy to Discriminate against Andreev Levels in a Majorana Fusion Experiment
Authors: Grabsch A. , Cheipesh Y. , Beenakker C. W. J.
Published: November 2019

Detection of the fusion rule of Majora na zero‐modes is a near‐term milestone on the road to topological quantum computation. An obstacle is that the non‐deterministic fusion outcome of topological zero‐modes can be mimicked by the merging of non‐topological Andreev levels. To distinguish these two scenarios, the dynamical signatures of the ground‐state degeneracy that is the defining property of non‐Abelian anyons is searched for. By adiabatically traversing parameter space along two different pathways, one can identify ground‐state degeneracies from the breakdown of adiabaticity. It is shown that the approach can discriminate against accidental degeneracies of Andreev levels.
Economic sustainability of heritage conservation in Hong Kong: The impact of heritage buildings on adjacent property prices
Authors: Kee Tristance , Chau K.W.
Published: November 2019

Informed by the theoretical framework of sustainable development and economic theories including the cluster theory and the corollary of the Coase Theorem, this paper empirically investigates the economic impact of architectural heritage in Hong Kong. Using the hedonic price model, the research examines the economic impact of 50 publicly owned versus 50 privately owned heritage buildings on adjacent residential property prices with a sample size of over 43,240 property transaction records spanning a time period of 10 years. The research supports that heritage conservation can promote economic sustainability aside from cultural sustainability and social engagement. This research benefits government policymakers, urban planners, architects, and heritage conservationists by contributing new knowledge to the studies on sustainable urban development, heritage conservation, and cultural economics.
Rheological Properties of Epoxy/Polypyrrole Coating and its Behavior as EMI Material
Authors: Pires Neto Jose Ferreira , Souto Loan Filipi Calheiro , Silva Adriana dos Anjos , Barra Guilherme Mariz de Oliveira , Naccache Monica Feijó , Soares Bluma Guenther , Sirqueira Alex da Silva
Published: November 2019

In this study, we analyze the rheological properties of epoxy/polypyrrole/carbon black coating and its performance as electromagnetic interference shielding efficiency (EMI SE). For this purpose, a commercial epoxy coating was mixed with a conductive polymer, namely polypyrrole. Rheological tests were performed to obtain the flow curve, the storage and loss moduli, the cure time and thixotropic characteristics. Thermal analysis of DSC (cure behavior) and EMI SE were also performed. Epoxy coating showed non‐Newtonian (shear thinning) behavior. The addition of PPy.DBSA reduced the coating fluidity by the increase in consistency index and viscosity. The stress oscillatory amplitude sweep test was performed to determine the linear viscoelastic range. The results of the LVR stress and strain frequency sweep tests were compared to the PPy.DBSA. The results show that LVR and critical crossover change with the percent of Polypyrrole. The cure times obtained by the rheometer and DSC were in good agreement: the addition of polypyrrole reduced the cure time, probably due to the presence of amino groups in the PPy.DBSA, which can react with the oxirane ring in the epoxy resin. The EMI SE attenuation by absorption and reflection mechanism was observed by adding 10 phr of PPy.DBSA. For practical applications, it is necessary to combine polypyrrole with conducting carbon black. The formulation with 1.5 phr of carbon black improves the EMI SE performance to 72%. J. VINYL ADDIT. TECHNOL., 26:348–353, 2020. © 2019 Society of Plastics Engineers