bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential expression of proteins in human prostate cancer tissues probed by MALDI imaging mass spectrometry
Authors: Mitra Amrita , Choubey Surya Kant , Das Rajdeep , Rout Pritilata , Sridhar T. S , Mishra Deepak , Mandal Amit Kumar 
Published: October 2020

AbstractHistopathology, the gold-standard method for diagnosis of human prostate cancer, is based on the analysis of changes in cellular morphology and tissue architecture in chemically stained tissue sections. Even at the very early stages of cancer with minimal phenotypic changes in cellular morphologies, there might be detectable changes in the expression profiles of proteins. Over the last decade, imaging mass spectrometry has been used to explore the spatial distribution and expression profiles of several molecules with their twodimensional heterogeneity retained across the tissue section. In the present study, using MALDI mass spectrometry based tissue imaging, we report the differential expression of three proteins, vinculin, ribonuclease T2 and 60 kDa heat shock protein across human prostate tissue sections in regions pathologically demarcated as frankly malignant. In an independent analysis, quantitative proteomics revealed that in cancerous prostate tissues, ribonuclease T2 and 60 kDa heat shock protein were significantly overexpressed by 22.26- and 6 folds respectively compared to benign condition. Our results show the utility of this approach to probe differential protein expression in architecturally intact cancer tissues. In addition, we propose that ribonuclease T2 and 60 kDa heat shock protein might be developed as diagnostic biomarkers for prostate cancer in future.
Associations between white matter hyperintensity burden, cerebral blood flow and transit time in small vessel disease: an updated meta-analysis
Authors: Stewart Catriona R , Stringer Michael S , Shi Yulu , Thrippleton Michael J , Wardlaw Joanna M 
Published: October 2020

AbstractCerebral small vessel disease is a major contributor to stroke and dementia, characterised by white matter hyperintensities (WMH) on neuroimaging. WMH are associated with reduced cerebral blood flow (CBF) cross-sectionally, though longitudinal associations remain unclear. We updated a 2016 meta-analysis, identifying 30 studies, 27 cross-sectional (n=2956) and 3 longitudinal (n=440), published since 2016. Cross-sectionally, we meta-analysed 10 new studies with 24 previously reported studies, total 34 (n=2180), finding lower CBF to be associated with worse WMH burden (mean global CBF: standardised mean difference: −0.45, 95% confidence interval (CI): −0.64,-0.27). Longitudinally, the association of baseline CBF with WMH progression varied: the largest study (5 years,n=252) found no associations, while another small study (4.5 years,n=52) found that low CBF in the periventricular WMH penumbra predicted WMH progression. We could not meta-analyse longitudinal studies due to different statistical and methodological approaches. We found lower CBF within WMH compared to normal appearing white matter (novel meta-analysis; 5 cross-sectional studies;n=295; SMD: −1.51, 95% CI: −1.94,-1.07). These findings highlight that relationships between resting CBF and WMH are complex and that more longitudinal studies analysing regional CBF and subsequent WMH change are required to determine the role of CBF in small vessel disease progression.
Organophosphate and organohalogen flame-retardant exposure and thyroid hormone disruption in a cohort of female firefighters and office workers from San Francisco
Authors: Trowbridge Jessica , Gerona Roy , McMaster Michael , Ona Katherine , Clarity Cassidy , Bessonneau Vincent , Rudel Ruthann , Buren Heather , Morello-Frosch Rachel 
Published: October 2020

AbstractBackgroundOccupational exposures to flame retardants (FR), which are suspected endocrine disrupting compounds, may be of particular concern for firefighters as they are commonly found in consumer products and have been detected in fire station dust and firefighter gear.ObjectivesThe Women Workers Biomonitoring Collaborative is a community based participatory research study that sought to measure environmental chemicals relevant to firefighting and evaluate their effects on thyroid hormone levels.MethodsWe measured 10 FR or their metabolites in urine of female firefighters and office workers from San Francisco: bis(1,3-dichloro-2-propyl) phosphate (BDCPP), bis(2-chloroethyl) phosphate (BCEP), dibutyl phosphate (DBuP), dibenzyl phosphate (DBzP), di-p-cresyl phosphate (DpCP), di-o-cresyl phosphate (DoCP), 2,3,4,5-tetrabromobenzoic acid (TBBA), tetrabromobisphenol-A (TBBPA), 5-OH-BDE 47, and 5-OH-BDE 100. We assessed potential predictors of exposure levels and the association between FR exposures and thyroxine (T4) and thyroid stimulating hormone (TSH).ResultsBDCPP, BCEP, and DBuP were the most commonly detected FRs, among all study participants, with intermediate BMI and college educated women having the highest levels, and Black women having higher BDCPP levels than White women. Firefighters had higher detection frequencies (DF) and exposure levels compared to office workers; median BDCPP levels were five times higher in firefighters than in office workers. Among firefighters, occupational activities were not significantly associated with FR levels, although position (i.e. officer and firefighter versus driver), being on-duty (versus off-duty) and assigned to the airport suggested a positive association with FR levels. Among firefighters, a doubling of BDCPP was associated with a 2.88% decrease (95%CI −5.28,-0.42) in T4. We did not observe significant associations between FR and T4 among office workers.DiscussionFirefighters had significantly higher exposures to FR compared to office workers, and we observed a negative association between BDCPP and thyroxine in firefighters. Future research should elucidate occupational sources of FR exposure and opportunities for exposure reduction.
Characterization of the signalling modalities of prostaglandin E2 receptors EP2 and EP4 reveals crosstalk and a role for microtubules
Authors: Vleeshouwers Ward , van den Dries Koen , de Keijzer Sandra , Joosten Ben , Lidke Diane S. , Cambi Alessandra 
Published: October 2020

AbstractProstaglandin E2 (PGE2) is a lipid mediator that modulates the function of myeloid immune cells such as macrophages and dendritic cells (DCs) through the activation of the G protein-coupled receptors EP2 and EP4. While both EP2 and EP4 signalling leads to an elevation of intracellular cyclic adenosine monophosphate (cAMP) levels through the stimulating Gαsprotein, EP4 also couples to the inhibitory Gαiprotein to decrease the production of cAMP. The receptor-specific contributions to downstream immune modulatory functions are still poorly defined. Here, we employed quantitative imaging methods to characterize the early EP2 and EP4 signalling events in myeloid cells and their contribution to the dissolution of adhesion structures called podosomes, which is a first and essential step in DC maturation. We first show that podosome loss in DCs is primarily mediated by EP4. Next, we demonstrate that EP2 and EP4 signalling leads to distinct cAMP production profiles, with EP4 inducing a transient cAMP response and EP2 inducing a sustained cAMP response only at high PGE2 levels. We further find that simultaneous EP2 and EP4 stimulation attenuates cAMP production, suggesting a reciprocal control of EP2 and EP4 signaling. Finally, we demonstrate that efficient signaling of both EP2 and EP4 relies on an intact microtubule network. Together, these results enhance our understanding of early EP2 and EP4 signalling in myeloid cells. Considering that modulation of PGE2 signalling is regarded as an important therapeutic possibility in anti-tumour immunotherapy, our findings may facilitate the development of efficient and specific immune modulators of PGE2 receptors.
The electrostatic allostery could be the trigger for the changes in dynamics for the PDZ domain of PICK1
Authors: Stevens Amy O. , He Yi 
Published: October 2020

ABSTRACTThe PDZ domain is a highly abundant protein-protein interaction domain that exists in many signaling proteins, such as PICK1. Despite the highly conserved structure of the PDZ family, the PDZ family has an extremely low sequence identity, making each PDZ domain unique. PICK1 is the only protein in the human genome that is comprised of a PDZ domain and a BAR domain. PICK1 regulates surface membrane proteins and has been identified as an integral player in drug addiction. Like many PDZ-containing proteins, PICK1 is positively regulated by its PDZ domain and has thus drawn attention to be a potential drug target to curb the effects of substance abuse. The goal of this study is to use all-atom molecular dynamics simulations and the electrostatic analysis program, DelPhi, to better understand the unique interactions and dynamic changes in the PICK1 PDZ domain upon complex formation. Our results demonstrated that the PICK1 PDZ domain shares similar canonical PDZ-ligand hydrogen bonding networks and fluctuations of the carboxylate-binding loop to other PDZ domains. Furthermore, our results are unique to the PICK1 PDZ domain as we reveal that the binding of ligand opens up the binding pocket and, at the same time, reduces the fluctuations of both the central part of the binding pocket and the short loop region between the αA-helix and βC-strand. More importantly, the binding of ligand resulted in charge redistribution at the binding pocket region as well as the N- and C-termini of the PDZ domain that are not a part of the binding pocket. These results suggest that the electrostatic allostery resulted from ligand binding could be the key factor leading to the changes in dynamics which may be associated with the activation of PICK1. Based on these results, an effective drug to target PDZ domain must not only stably bind to the PICK1 PDZ domain but also prevent the electrostatic allostery of the PDZ domain.
How does mobility affect social media advertising effectiveness? A study in WeChat
Authors: Zhang Yanping , Li Xiaodong , Hamari Juho 
Published: October 2020

PurposeThis study aims to investigate how aspects of mobility affect social media advertising effectiveness (i.e. consumer purchase intention) on mobile platforms from the perspective of the fit-viability model.Design/methodology/approachData were collected through an online questionnaire survey of 378 WeChat users and used to test hypotheses with structural equation modeling.FindingsConsumer purchase intention is significantly positively influenced by time flexibility, spatial flexibility, mobile lifestyle and ad relevance. Meanwhile, ambivalence toward ads mediates the relationships of time flexibility and spatial flexibility with purchase intention and moderates the relationships of mobile lifestyle and ad relevance with purchase intention.Research limitations/implicationsThe findings offer researchers and practitioners a new angle to understand advertising effectiveness on mobile social media and extend the application of the fit-viability model.Originality/valueThis paper fills the research gap on the role of mobility in social media advertising.
Do the brand and packaging matter? The case of hotel bathroom amenities
Authors: Jeong Miyoung , Kubickova Marketa 
Published: October 2020

PurposeCreating memorable experiences for customers at the individual property is one of the primary goals in hotel management across all segments. Adopting the concept of the ingredient branding, this study aims to attempt to identify the effects of bathroom amenity brands on customers' attitudes toward the hotel brand image and their behavior intentions toward a hotel brand. Specifically, this study assesses the importance of bathroom amenities on customer experience. It also examines the effects of bathroom amenity and their sustainable practices on hotel brand image and behavior intentions. Lastly, it provides suggestions for hoteliers in selecting right and appealing bathroom amenities while enhancing customers' hotel experience.Design/methodology/approachThis study employed a 3 (hotel service level: economy, midscale, vs luxury) × 2 (bathroom amenity brand: luxury vs general) × 2 (bathroom amenity packaging: bottle vs dispenser) between-subjects experimental design. A total of 557 useable surveys were obtained to test the study's hypotheses.FindingsThe results reveal that customers had a better hotel image when high-end brand bathroom amenities in a bottle were offered. Specifically, when economy hotels provided high-end brand bathroom amenities, customers had a better hotel image, which lead to strong return intentions. Typically, bathroom amenities in the bottle were perceived better than those in the dispenser when it came to the hotel image.Practical implicationsThe findings of this study reconfirm that the level of hotel service, bathroom amenity brand and bathroom amenity packaging jointly affect hotels' overall image. Specifically, the generic bathroom amenity in the dispenser somewhat degrades the image of the hotel for economy hotels; however, the image of hotel is not significantly affected by the type of bathroom packaging when the hotel has luxury bathroom amenities. Thus, hotel management should pay more attention to selecting the bathroom amenity brand, which can offer more memorable experience for customers.Originality/valueLittle research has been documented on the effects of hotel bathroom amenity brands on customers' attitudes toward hotel brand image and their psychological behaviors in the hotel industry, lacking rigorous theoretical examinations. The current study provides several important contributions not only to the body of knowledge but to the hotel industry.
Reduced to the max: firm performance and organizational ambidexterity research
Authors: Meisinger Norman , Moldaschl Manfred 
Published: October 2020

PurposeFor nearly three decades, numerous scholars have searched for a robust relationship between firm performance and organizational ambidexterity—so far with questionable results. The aim of this short essay is thus to critically examine the performance of applied performance measurements.Design/methodology/approachAfter discussing methodological issues and revealing a conceptually neglected “level” distinction in organizational ambidexterity studies, we contribute to conceptual clarity as to whether exploration and exploitation ought to be conceived as continuous or orthogonal.FindingsFirst, even if the dichotomy of exploration and exploitation is orthogonally conceptualized, at least one trade-off, either on the level of the explanans or the level of the explanandum, can be bypassed but cannot conceptually be denied. Second, we conclude that explaining overall firm performance with the relation of just two variables (exploration and exploitation)—referring to the inherently conflicting title of this paper, “Reduced to the Max”—is a hazardous endeavor.Research limitations/implicationsBased on these insights, future research may benefit from studying organizational ambidexterity and firm performance more qualitatively and paying more attention to the declared level distinction.Originality/valueThe paper reveals a crucial neglect of level and provides an answer to one of the core questions of organizational ambidexterity research: that of continuity vs orthogonality.
The role of public debt on economic growth with capital loss
Authors: Tran Nhat Thien 
Published: October 2020

AbstractThis paper studies some models in which the “engine of growth” is public debt and capital accumulation. Public debt is assumed to be driven by domestic debt and external debt. The study shows that debt will support economic growth if the initial level of productivity is greater than the cost of investment. In an economy with and without the loss of capital, the article shows the existence of a unique optimal share of investment in physical and human capital and/or new technology. Moreover, if the productivity of the first period is lower than that of a defined threshold value then there exists an optimal level of debt. In addition, if the productivity of the first period is greater than or equal to a defined threshold value, the bigger the debt, the better economies become. Furthermore, this study shows that in an economy with capital loss there is a hidden overhead equivalent to an artificially‐augmented interest rate.
Promoting Social Sustainability of Urban Neighbourhoods: The Case of Bethnal Green, London
Authors: Shirazi M. Reza , Keivani Ramin , Brownill Sue , Butina Watson Georgia 
Published: October 2020

AbstractThe growing significance of neighbourhoods in the urban planning discipline, alongside increasing attention to the social dimension of sustainable communities and societies, has brought to the fore the need to conceptualize socially sustainable neighbourhoods. In this article we reflect critically on the concept of socially sustainable neighbourhoods in two areas, namely definition and operationalization. We then propose a tripartite framework for measuring social sustainability of urban neighbourhoods, which combines the three elements of neighbourhood, neighbouring and neighbours. This framework is tested, examined and discussed for the case of Bethnal Green, London. We then integrate our findings into a social sustainability enhancement index, which encompasses practical recommendations to promote the social sustainability of Bethnal Green. We conclude this article by highlighting the research and policy implications of the proposed framework, and making suggestions for improving the methodology of future research.
Population parameters and growth ofRiptortus pedestris(Fabricius) (Hemiptera: Alydidae) under elevated CO2concentrations
Authors: Ahn Jeong Joon , Choi Kyung San , Koh Sangwook 
Published: October 2020

AbstractWe evaluated the direct effects of three different CO2concentrations (400, 600 and 1,000 ppm) on the population parameters and growth of the bean bug,Riptortus pedestris,while being fed on soybean. The raw life history data fromR. pedestriswas analyzed using an age‐stage, two‐sex life table to take the viable development rate among individuals into account. Based on the age‐stage, two‐sex life table analysis, the population projections ofR. pedestrisprovide the stage structure and variability of the population growth under different CO2treatments. Our results showed significantly shorter immature durations and higher pre‐adult survival rate under elevated CO2(1,000 ppm) than those under ambient CO2(400 ppm). The population ofR. pedestrisreared under elevated CO2conditions showed higher intrinsic and finite rates of increase but a lower mean generation time thanR. pedestrisreared under ambient CO2conditions. Our results show the population parameters and growth ofR. pedestrisare influenced by increased CO2relative to ambient CO2treatment. Further studies on the long‐term direct effects of different CO2levels onR. pedestrisare essential to understand their population dynamics and to establish appropriate management strategies.
Phase II study of durvalumab and tremelimumab in pulmonary sarcomatoid carcinoma: KCSG‐LU16‐07
Authors: Kim Miso , Keam Bhumsuk , Ock Chan‐Young , Kim Se Hyun , Kim Yu Jung , Lim Sun Min , Kim Jin‐Soo , Kim Tae Min , Hong Sook‐Hee , Ahn Mi Sun , Shin Seong Hoon , Kang Eun Joo , Kim Dong‐Wan , Im Sun‐Wha , Kim Jong‐Il , Lee Jong Seok , Kim Joo‐Hang , Heo Dae Seog 
Published: October 2020

BackgroundPulmonary sarcomatoid carcinoma (PSC) is rare with a poor outcome and is resistant to conventional cytotoxic chemotherapy. The efficacy and safety of durvalumab and tremelimumab for treating recurrent or metastatic PSCs were assessed by a nonrandomized, open‐label, phase II study.MethodsA total of 18 patients with recurrent or metastatic PSC received 1500 mg of durvalumab and 75 mg of tremelimumab every four weeks, followed by 750 mg of durvalumab every two weeks until the disease progressed, or an unacceptable toxicity level was reached. The primary endpoint was the objective response rate (ORR). The secondary endpoints were progression‐free survival (PFS), overall survival (OS), and toxicity. Genomic profiling of PSC by next‐generation sequencing (NGS) and determination of peripheral blood lymphocyte subsets using flow cytometry were performed for exploratory analysis.ResultsA total of 15 out of 18 patients were evaluated for the analysis of the primary endpoint. At the data cutoff point, the ORR of 26.7% (95% confidence interval [CI]: 7.8–55.1) was achieved with the median follow‐up duration of 12.0 months (range, 8.4–16.1). Median PFS and OS were 5.9 months (95% CI: 1.1–11.9) and 15.4 months (95% CI: 11.1‐not reached), respectively. Treatment‐related adverse events (AEs) of any grade were reported in 16 patients; the most common AEs were pruritus (n = 5), pneumonitis (n = 4), and rash (n = 4). Treatment was discontinued in two patients due to AEs of grade ≥ 3.ConclusionsDurvalumab and tremelimumab demonstrated clinical benefit with a prolonged survival and manageable toxicity profile in patients with recurrent or metastatic PSC.
Unforeseen consequences of conservation management practices: case study on herding rhino as an anti‐poaching measure
Authors: Fàbregas María C. , Fosgate Geoffrey T. , Ganswindt André , Bertschinger Henk , Meyer Leith C. R. 
Published: October 2020

AbstractThe current biodiversity crisis calls for effective conservation measures. However, some measures may have unforeseen negative consequences on individual species. Herding, a management practice currently used in some wildlife species to protect animals from poachers, can cause habituation to humans, which unintentionally might increase their risk of being poached at a later time. Herding could also negatively impact animal welfare and physiology when perceived as a stressor, with potential negative consequences at the individual and population level. In this study, we tested the following hypotheses: 1) herding elicits habituation to humans in white rhino, and 2) this practice affects the behavior and physiological state of rhino, but they can habituate to it. To that aim, we investigated the effects of herding on the response of rhino to initially unfamiliar people, expression of aggressive and discomfort behaviors, and fecal glucocorticoid metabolite (fGCM) concentrations (a commonly used indicator of physiological stress) in two cohorts of six and 10 semi‐wild orphan white rhino. Rhino did not interrupt their activity to an approaching person on foot (99%) or in a vehicle (94%), indicating habituation to humans. Aggressive and discomfort behaviors were displayed more often while being herded, and their frequency increased significantly with increasing herding pressure. Finally, overall mean fGCM concentrations were 16.1% higher under herding compared to non‐herding conditions, but individual fGCM levels varied up to 17‐fold under each scenario, suggesting that herding might not elicit a physiological stress response in these animals. While rhino security is paramount in the current poaching crisis, management practices must ensure that they do not impact negatively at the individual and population level.