bluuebunny/crossref_metadata_2025_split huggingface dataset:
Silent mating‐type information regulation 2 homolog 1 overexpression is an important strategy for the survival of adapted suspension tumor cells
Authors: Park Ji Young , Han Sora , Ka Hye In , Joo Hyun Jeong , Soh Su Jung , Yoo Kyung Hyun , Yang Young 
Published: July 2019

AbstractCharacterization of circulating tumor cells (CTC) is important to prevent death caused by the metastatic spread of cancer cells because CTC are associated with distal metastasis and poor prognosis of breast cancer. We have previously developed suspension cells (SC) using breast cancer cell lines and demonstrated their high metastatic potential. As survival of CTC is highly variable from a few hours to decades, herein we cultured SC for an extended time and named them adapted suspension cells (ASC). Silent mating‐type information regulation 2 homolog 1 (SIRT1) expression increased in ASC, which protected the cells from apoptosis. High SIRT1 expression was responsible for the suppression of nuclear factor kappa B (NF‐κB) activity and downregulation of reactive oxygen species (ROS) in ASC. As the inhibition of NF‐κB and ROS production in SIRT1‐depleted ASC contributed to the development of resistance to apoptotic cell death, maintenance of a low ROS level and NF‐κB activity in ASC is a crucial function of SIRT1. Thus, SIRT1 overexpression may play an important role in growth adaptation of SC because SIRT1 expression is increased in long‐term rather than in short‐term cultures.
Allergic contact dermatitis in atopic individuals: Results of a 30‐year retrospective study
Authors: Teo Ying , McFadden John P. , White Ian R. , Lynch Magnus , Banerjee Piu 
Published: July 2019

AbstractBackgroundThe association between atopic dermatitis (AD) and contact allergy, remains unclear, with studies to date showing conflicting results.ObjectivesTo investigate the prevalence of contact allergy in AD individuals compared to those without AD.MethodsResults of 46 250 patients patch tested in a single centre over a span of 30 years were reviewed, comparing those with AD with those without AD. Collected data were analysed with corrections for multiple confounding variables, including date of patch testing to account for changes in allergens tested over the period.ResultsNine allergens showed a statistically significant difference between the two groups. Contact allergy to nickel, cobalt and primin was less likely to arise in those with AD, whilst substances found in topical dermatological products were more likely to be associated with AD.ConclusionsThis is the largest single centre study of contact sensitization in atopy reported to date. The previously reported association between contact allergy to sesquiterpene lactone and AD is reinforced. The decreased incidence of metal allergy suggests distinct immunological effector mechanisms in sensitization to these allergens. In keeping with previous publications, exposure to topical treatments for AD can result in sensitisation and contact allergy and clinicians should consider patch testing in AD individuals who report worsening of their skin despite continued treatment with topical medicaments.
Caspase‐3‐mediated GSDME activation contributes to cisplatin‐ and doxorubicin‐induced secondary necrosis in mouse macrophages
Authors: Mai Feng‐Yi , He Pengyan , Ye Jie‐Zhou , Xu Li‐Hui , Ouyang Dong‐Yun , Li Chen‐Guang , Zeng Qiong‐Zhen , Zeng Chen‐Ying , Zhang Cheng‐Cheng , He Xian‐Hui , Hu Bo 
Published: July 2019

AbstractObjectiveInduction of secondary necrosis/pyroptosis contributes to the toxicity of chemotherapeutic drugs, in which gasdermin E (GSDME) plays critical roles. This study aimed to explore whether GSDME is involved in mediating the cytotoxic effects of cisplatin and doxorubicin on mouse macrophages.MethodsRAW 264.7 cells and bone marrow‐derived macrophages (BMDMs) were treated with cisplatin or doxorubicin. Propidium iodide staining was used to assay necrosis, and immunoblotting was performed to detect protein expression. GSDME was knocked down by using small interfering RNA. Mice were injected intraperitoneally to evaluate toxicity to macrophages in vivo. Flow cytometry and immunofluorescence microscopy were adopted to analyse phenotypes of peritoneal cells. Cytokine levels were assayed by cytometric bead array.ResultsBoth cisplatin and doxorubicin dose‐dependently induced necrosis in mouse RAW 264.7 macrophages and BMDMs. Accompanying this, multiple caspases were activated, concomitant with the cleavage of poly (ADP‐ribose) polymerase. Consistent with caspase‐3 activation, GSDME was cleaved to generate its N‐terminal fragment (GSDME‐NT), thus leading to secondary necrosis/pyroptosis. Inhibition of caspase‐3 significantly attenuated the generation of GSDME‐NT concurrently with decreased necrosis in macrophages. GSDME knockdown also evidently decreased the necrosis in RAW 264.7 and BMDMs. Besides, cisplatin administration depleted peritoneal macrophages in mice, which was associated with caspase‐3 activation and GSDME‐NT generation. Consistent with the macrophage depletion, cisplatin administration significantly decreased survival of mice with bacterial infection.ConclusionChemotherapeutic cisplatin and doxorubicin exerted their cytotoxicity on macrophages partly by inducing caspase‐3/GSDME‐mediated secondary necrosis.
Increased pulmonary artery diameter is associated with reduced FEV1 in former World Trade Center workers
Authors: de la Hoz Rafael E. , Jeon Yunho , Reeves Anthony P. , San José Estépar Raúl , Liu Xiaoyu , Doucette John T. , Celedón Juan C. , Nolan Anna 
Published: July 2019

AbstractRationaleOccupational exposures at the WTC site after September 11, 2001 have been associated with several presumably inflammatory lower airway diseases. Pulmonary arterial enlargement, as suggested by an increased ratio of the diameter of the pulmonary artery to the diameter of the aorta (PAAr) has been reported as a computed tomographic (CT) scan marker of adverse respiratory health outcomes, including WTC‐related disease. In this study, we sought to utilize a novel quantitative CT (QCT) measurement of PAAr to test the hypothesis that an increased ratio is associated with FEV1 below each subject's statistically determined lower limit of normal (FEV1 < LLN).MethodsIn a group of 1,180 WTC workers and volunteers, we examined whether FEV1 < LLN was associated with an increased QCT‐measured PAAr, adjusting for previously identified important covariates.ResultsUnadjusted analyses showed a statistically significant association of FEV1 < LLN with PAAr (35.3% vs 24.7%, P = 0.0001), as well as with height, body mass index, early arrival at the WTC disaster site, shorter WTC exposure duration, post‐traumatic stress disorder checklist (PCL) score, wall area percent and evidence of bronchodilator response. The multivariate logistic regression model confirmed the association of FEV1 < LLN with PAAr (OR 1.63, 95% CI 1.21, 2.20, P = 0.0015) and all the unadjusted associations, except for PCL score.ConclusionsIn WTC workers, FEV1 < LLN is associated with elevated PAAr which, although likely multifactorial, may be related to distal vasculopathy, as has been hypothesized for chronic obstructive pulmonary disease.
ARCHAEOMUSICA – Making the Past Audible
Authors: Both Arnd Adje 
Published: July 2019

AbstractThe author addresses the challenge and possible solutions related to museum display of archaeological sounds and music in museum contexts. By reflecting on his own work as a curator, the author illustrates his approach through examples drawn from the travelling exhibition ARCHAEOMUSICA – The Sounds and Music of Ancient Europe. The exhibition was presented in a variety of museums between 2016 and 2018.
Pain or Gain? Chinese Experience of Capital Account Liberalization
Authors: Peng Hongfeng , Yu Jingwen 
Published: July 2019

AbstractThe neoclassical growth model predicts that capital account liberalization could potentially enhance economic performance; however, there is no consistent empirical evidence to support this positive association. Using a novel dataset of Chinese capital account openness, this paper demonstrates a positive relationship between capital account liberalization and aggregate economic performance. The difference‐indifferences method is used to capture the causal effect of capital account liberalization on economic performance by taking advantage of variations in both external financial dependence and the progress of capital account openness. We investigate three channels that could strengthen this positive relationship using a firm‐level dataset. We find that capital account liberalization could: (i) alleviate the degree of resource misallocation, and this effect is more significant in industries relying heavily on external finance and in regions with more favorable business environments; (ii) enhance firms’ total factor productivity; and (iii) promote innovation. Our findings suggest that a strategy of gradual openness will leave some leeway not only for improvement in domestic markets but also to mitigate exposure to unfavorable global shocks.
Medical and non‐medical cannabis use and risk of prescription opioid use disorder: Findings from propensity score matching
Authors: Liang Di , Wallace Mark S. , Shi Yuyan 
Published: July 2019

AbstractIntroduction and AimsPrevious research suggested that cannabis use was associated with increased risks of prescription opioid misuse and use disorder. This study examined whether these associations differed by cannabis use purpose.Design and MethodsThis is a secondary analysis of cross‐sectional surveys with propensity score matching. Medical cannabis users (N = 1295), cannabis dual users with both medical and non‐medical purposes (N = 707) and non‐medical cannabis users (N = 18 666) were compared with cannabis non‐users (N = 57 196) in the pooled 2013–2016 US nationally representative National Survey on Drug Use and Health. Propensity score models were applied to match cannabis non‐users to cannabis users with different purposes with respect to potential confounders in individual socioeconomic characteristics, other substance use disorders and health conditions. In a matched sample, logistic regressions were used to assess associations.ResultsPropensity score matching considerably improved the balance of the potential confounders between cannabis non‐users and users. In a matched sample, non‐medical cannabis use was associated with increased risks of prescription opioid misuse (OR = 3.15, 95%CI: 2.89–3.44) and use disorder (OR = 2.52, 95%CI: 2.06–3.10). Cannabis dual use and medical cannabis use were associated with increased risks of prescription opioid misuse (OR = 2.55, 95%CI: 1.78–3.65; OR = 2.15, 95%CI: 1.58–2.91, respectively), but they were not associated with prescription opioid use disorder.Discussion and ConclusionsMedical and non‐medical cannabis use both were both associated with increased risks of prescription opioid misuse. Medical cannabis use, however, was not associated with prescription opioid use disorder, and non‐medical cannabis was. There appeared to be differential associations between cannabis use and prescription opioid use disorder by cannabis use purpose.
Towards a unified framework for connectivity that disentangles movement and mortality in space and time
Authors: Fletcher Robert J. , Sefair Jorge A. , Wang Chao , Poli Caroline L. , Smith Thomas A. H. , Bruna Emilio M. , Holt Robert D. , Barfield Michael , Marx Andrew J. , Acevedo Miguel A. 
Published: July 2019

AbstractPredicting connectivity, or how landscapes alter movement, is essential for understanding the scope for species persistence with environmental change. Although it is well known that movement is risky, connectivity modelling often conflates behavioural responses to the matrix through which animals disperse with mortality risk. We derive new connectivity models using random walk theory, based on the concept of spatial absorbing Markov chains. These models decompose the role of matrix on movement behaviour and mortality risk, can incorporate species distribution to predict the amount of flow, and provide both short‐ and long‐term analytical solutions for multiple connectivity metrics. We validate the framework using data on movement of an insect herbivore in 15 experimental landscapes. Our results demonstrate that disentangling the roles of movement behaviour and mortality risk is fundamental to accurately interpreting landscape connectivity, and that spatial absorbing Markov chains provide a generalisable and powerful framework with which to do so.
Prospective study of the additional benefit of plexus magnetic resonance imaging in the diagnosis of chronic inflammatory demyelinating polyneuropathy
Authors: Jomier F. , Bousson V. , Viala K. , Péréon Y. , Magot A. , Cauquil C. , Bouhour F. , Vial C. , Bedat‐Millet A.‐L. , Taithe F. , Bresch S. , Siri A. , Kubis N. , Lozeron P. 
Published: July 2019

Background and purposeHypertrophy/signal hyperintensity and/or gadolinium enhancement of plexus structures on magnetic resonance imaging (MRI) are observed in two‐thirds of cases of typical chronic inflammatory demyelinating polyneuropathy (CIDP). The objective of our study was to determine the additional benefit of plexus MRI in patients referred to tertiary centers with baseline clinical and electrophysiological characteristics suggestive of typical or atypical CIDP.MethodsA total of 28 consecutive patients with initial suspicion of CIDP were recruited in nine centers and followed for 2 years. Plexus MRI data from the initial assessment were reviewed centrally. Physicians blinded to the plexus MRI findings established the final diagnosis (CIDP or neuropathy of another cause). The proportion of patients with abnormal MRI was analyzed in each group.ResultsChronic inflammatory demyelinating polyneuropathy was confirmed in 14 patients (50%), as were sensorimotor CIDP (n = 6), chronic immune sensory polyradiculoneuropathy (n = 2), motor CIDP (n = 1) and multifocal acquired demyelinating sensory and motor neuropathy (n = 5). A total of 37 plexus MRIs were performed (17 brachial, 19 lumbosacral and 8 in both localizations). MRI was abnormal in 5/37 patients (14%), all of whom were subsequently diagnosed with CIDP [5/14(36%)], after an atypical baseline presentation. With plexus MRI results masked, non‐invasive procedures confirmed the diagnosis of CIDP in all but one patient [1/14 (7%)]. Knowledge of the abnormal MRI findings in the latter could have prevented nerve biopsy being performed.ConclusionSystematic plexus MRI in patients with initially suspected CIDP provides little additional benefit in confirming the diagnosis of CIDP.
Recent insights into the genotype–phenotype relationship from massively parallel genetic assays
Authors: Kemble Harry , Nghe Philippe , Tenaillon Olivier 
Published: July 2019

AbstractWith the molecular revolution in Biology, a mechanistic understanding of the genotype–phenotype relationship became possible. Recently, advances in DNA synthesis and sequencing have enabled the development of deep mutational scanning assays, capable of scoring comprehensive libraries of genotypes for fitness and a variety of phenotypes in massively parallel fashion. The resulting empirical genotype–fitness maps pave the way to predictive models, potentially accelerating our ability to anticipate the behaviour of pathogen and cancerous cell populations from sequencing data. Besides from cellular fitness, phenotypes of direct application in industry (e.g. enzyme activity) and medicine (e.g. antibody binding) can be quantified and even selected directly by these assays. This review discusses the technological basis of and recent developments in massively parallel genetics, along with the trends it is uncovering in the genotype–phenotype relationship (distribution of mutation effects, epistasis), their possible mechanistic bases and future directions for advancing towards the goal of predictive genetics.
The interplay of protein–ligand and water‐mediated interactions shape affinity and selectivity in the LAO binding protein
Authors: Vergara Renan , Romero‐Romero Sergio , Velázquez‐López Isabel , Espinoza‐Pérez Georgina , Rodríguez‐Hernández Annia , Pulido Nancy O. , Sosa‐Peinado Alejandro , Rodríguez‐Romero Adela , Fernández‐Velasco Daniel Alejandro 
Published: July 2019

The study of binding thermodynamics is essential to understand how affinity and selectivity are acquired in molecular complexes. Periplasmic binding proteins (PBPs) are macromolecules of biotechnological interest that bind a broad number of ligands and have been used to design biosensors. The lysine‐arginine‐ornithine binding protein (LAO) is a PBP of 238 residues that binds the basic amino acids l‐arginine and l‐histidine with nm and μm affinity, respectively. It has been shown that the affinity difference for arginine and histidine binding is caused by enthalpy, this correlates with the higher number of protein–ligand contacts formed with arginine. In order to elucidate the structural bases that determine binding affinity and selectivity in LAO, the contribution of protein–ligand contacts to binding energetics was assessed. To this end, an alanine scanning of the LAO‐binding site residues was performed and arginine and histidine binding were characterized by isothermal titration calorimetry and X‐ray crystallography. Although unexpected enthalpy and entropy changes were observed in some mutants, thermodynamic data correlated with structural information, especially, the binding heat capacity change. We found that selectivity is conferred by several residues rather than exclusive arginine–protein interactions. Furthermore, crystallographic structures revealed that protein–ligand contributions to binding thermodynamics are highly influenced by the solvent. Finally, we found a similar backbone conformation in all the closed structures obtained, but different structures in the open state, suggesting that the binding site residues of LAO play an important role in stabilizing not only the holo conformation, but also the apo state.DatabaseStructural data are available in the Protein Data Bank database under the accession numbers 6MLE, 6MLN, 6MLG, 6MKX, 6MLI, 6MLA, 6MKU, 6MKW, 6ML0, 6MLD, 6MLV, 6MLO, 6MLP, 6ML9, 6MLJ.
Measuring the symptomatic, physical, emotional and social impacts of dry mouth: A qualitative study
Authors: Gibson Barry , Periyakaruppiah Karthik , Thornhill Martin H. , Baker Sarah R. , Robinson Peter G. 
Published: July 2019

AbstractObjectiveTo explore the impacts of dry mouth in order to develop a comprehensive condition‐specific OHRQoL measure.BackgroundDry mouth has been shown to have significant, if not more severe impacts on OHRQoL, than dental caries. Yet there remain few studies reporting on how to develop a comprehensive measure of the impact of dry mouth on OHRQoL.MethodsThis study was a qualitative study using semi‐structured interviews. Data were collected from a purposive sample of 17 people with dry mouth (14 women, three men). The sample was drawn to capture a comprehensive range of impacts of dry mouth. These interviews were analysed using a framework approach informed by existing functionalist approaches to OHRQoL.ResultsParticipants reported a huge range of symptoms associated with perceived dry mouth resulting in extensive impacts on physical, emotional (psychological) and social functioning. Dry mouth could also result in restrictions in social participation which, under some conditions, could be disabling. These impacts were modified by psychological, social and environmental factors.ConclusionsIf we are to measure the impacts of oral conditions, it is important that this is done systematically and with reference to existing conceptual models of health. Current measures of the impact of dry mouth cover symptoms, discomfort and physical impacts along with some aspects of how people cope with the condition. This study proposes a more comprehensive approach that includes the full range of impacts people experience. Such an approach may enable us to focus on “downstream” and “upstream” interventions for dry mouth.
Real‐world effects of long‐term rifaximin treatment for Japanese patients with hepatic encephalopathy
Authors: Suzuki Hiroyuki , Sezaki Hitomi , Suzuki Fumitaka , Kasuya Kayoko , Sano Tomoya , Fujiyama Shunichiro , Kawamura Yusuke , Hosaka Tetsuya , Akuta Norio , Saitoh Satoshi , Kobayashi Masahiro , Arase Yasuji , Ikeda Kenji , Suzuki Yoshiyuki , Kumada Hiromitsu 
Published: July 2019

AimRifaximin (RFX) improves hepatic encephalopathy (HE). However, information on long‐term treatment with RFX is limited. In this study, we aimed to investigate the effect of long‐term treatment with RFX on HE and liver function. Moreover, we investigated factors associated with the recurrence of HE under RFX treatment.MethodsIn this retrospective cohort study, we consecutively enrolled 65 patients with HE who initiated RFX treatment (1200 mg/day) in our hospital from January 2017 to June 2018. We evaluated liver function test results, including blood ammonia levels, and the recurrence rate of HE after RFX treatment.ResultsThe median follow‐up duration was 41.6 weeks (range, 1.4–96.7 weeks). The blood ammonia level significantly declined from 157 to 86 μg/dL at 4 weeks after RFX treatment (P < 0.01), and the effect was prolonged. Furthermore, Child–Pugh score decreased in 51% (26/51) of the patients at 12 weeks during RFX treatment. The recurrence rate of HE after RFX treatment was 26.2% (17/65), and presence of ascites at baseline was identified as the only independent risk factor for HE recurrence (hazard ratio 4.71; 95% confidence interval, 1.27–17.5; P = 0.02). The cumulative recurrence rate of HE was significantly lower in patients without ascites than in patients with ascites at baseline (13.8% vs. 50.8%, P = 0.001).ConclusionsLong‐term treatment with RFX was beneficial for HE and liver function in patients with HE. Furthermore, the recurrence rate of HE was low in RFX‐treated patients without ascites. Thus, long‐term treatment with RFX could be effective for the management of Japanese patients with HE.
Distinct genetic alterations and luminal molecular subtype in nested variant of urothelial carcinoma
Authors: Weyerer Veronika , Weisser Rebecca , Moskalev Evgeny A , Haller Florian , Stoehr Robert , Eckstein Markus , Zinnall Ulrike , Gaisa Nadine T , Compérat Eva , Perren Aurel , Keck Bastian , Allory Yves , Kristiansen Glen , Wullich Bernd , Agaimy Abbas , Hartmann Arndt , Bertz Simone 
Published: July 2019

AimsNested variant of urothelial carcinoma (NVUC) is rare, and only a few small series exist. Molecular characteristics and the classifying marker profile as well as therapeutic targets of this specific variant are mostly unknown. The aim of this study was to characterise NVUC at the molecular level in one of the largest cohorts to date. In addition, we applied an immunohistochemical marker panel in order to define the molecular subtype.Methods and resultsSixty NVUC cases were collected from different departments. TERT promoter mutation analysis was carried out in all samples using SNaPshot analysis. Targeted sequencing of 48 cancer‐related genes by next‐generation sequencing (NGS) analysis was performed in a subset of 26 cases. Immunohistochemical markers CD44, CK5, CK14, EGFR, p63, FOXA1, GATA3, CD24 and CK20 were used to elucidate the molecular subtype. A total of 62.5% of NVUC cases harboured a mutation of the TERT promoter. Additionally, TP53, JAK3 and CTNNB1 were among the most frequently mutated genes identified by NGS analysis. Subtyping revealed that all NVUC express luminal markers such as CD24, FOXA1, GATA3 and CK20.ConclusionsIn summary, NVUC belong to the luminal molecular subtype. Moreover, a subset of NVUC seems to be characterised by mutations of the Wnt and inflammatory pathways, including JAK3 mutations, indicating a different biological background compared to conventional urothelial bladder cancer.